The Experts below are selected from a list of 1593 Experts worldwide ranked by ideXlab platform
Jian-dong Huang - One of the best experts on this subject based on the ideXlab platform.
-
Specific depletion of the motor protein KIF5B leads to deficits in dendritic transport, synaptic plasticity and memory
eLife, 2020Co-Authors: Junjun Zhao, Pui-yi Kwan, Hei-lok Chan, Louisa Hoi-ying Lo, Ying-shing Chan, Wing-ho Yung, Jian-dong HuangAbstract:Transporting molecules within a cell becomes a daunting task when the cell is a neuron, with fibers called axons and dendrites that can stretch as long as a meter. Neurons use many different molecules to send messages across the body and store memories in the brain. If the right molecules cannot be delivered along the length of nerve cells, connections to neighboring neurons may decay, which may impair learning and memory. Motor proteins are responsible for transporting molecules within cells. Kinesins are a type of motor protein that typically transports materials from the body of a neuron to the cell’s periphery, including the dendrites, which is where a neuron receives messages from other nerve cells. Each cell has up to 45 different kinesin motors, but it is not known whether each one performs a distinct task or if they have overlapping roles. Now, Zhao, Fok et al. have studied two similar kinesins, called KIF5A and KIF5B, in rodent neurons to determine their roles. First, it was shown that both proteins were found at dendritic spines, which are small outgrowths on dendrites where contact with other cells occurs. Next, KIF5A and KIF5B were depleted, one at a time, from neurons extracted from a brain region called the hippocampus. Removing KIF5B interfered with the formation of dendritic spines, but removing KIF5A did not have an effect. Dendritic spines are essential for learning and memory, so several behavioral tests were conducted on mice that had been genetically modified to express less KIF5B in the forebrain. These tests revealed that the mice performed poorly in tasks that tested their memory recall. This work opens a new area of research studying the specific roles of different kinesin motor proteins in nerve cells. This could have important implications because certain kinesin motor proteins such as KIF5A are known to be defective in some inherited neurodegenerative diseases.
-
KIF5B modulates central spindle organization in late stage cytokinesis in chondrocytes
Cell & Bioscience, 2019Co-Authors: Danny Chan, Jian-dong Huang, Kathryn S E CheahAbstract:The growth plate is a special region of the cartilage that drives longitudinal growth of long bones. Proliferating chondrocytes in the growth plate, arranged in columns, divide perpendicular to the long axis of the growth plate then intercalate to re-align with parental columns. Which molecular partners maintain growth plate columnar structures and chondrocyte cytokinesis has not been fully revealed. It is reported that kinesin family member 3A (KIF3A), a subunit of kinesin-2, plays an important role in maintaining columnar organization in growth plates via controlling primary cilia formation and cell proliferation. Here we identify kinesin family member 5B (KIF5B), the heavy chain of kinesin-1, a ubiquitously expressed motor protein for anterograde intracellular transport along the microtubule network, as a key modulator of cytokinesis in chondrocytes via maintenance of central spindle organization. We show that KIF5B is concentrated in the central spindle during cytokinesis in both primary chondrocytes and chondrogenic ATDC5 cells. The failure of cytokinesis in KIF5B null chondrocytes leads to incomplete cell rotation, disrupting proliferation and differentiation, and results in a disorganized growth plate.
-
Kinesin-1 Is a New Actor Involved in Platelet Secretion and Thrombus Stability.
Arteriosclerosis Thrombosis and Vascular Biology, 2018Co-Authors: Frédéric Adam, Jian-dong Huang, Alexandre Kauskot, Mathieu Kurowska, Nicolas Goudin, Isabelle Munoz, Jean-claude Bordet, Marijke Bryckaert, Alain Fischer, Delphine BorgelAbstract:Objective— Platelet secretion is crucial for many physiological platelet responses. Even though several regulators of the fusion machinery for secretory granule exocytosis have been identified in platelets, the underlying mechanisms are not yet fully characterized. Approach and Results— By studying a mouse model (cKO [conditional knockout] KIF5B ) lacking KIF5B (kinesin-1 heavy chain) in its megakaryocytes and platelets, we evidenced unstable hemostasis characterized by an increase of blood loss associated to a marked tendency to rebleed in a tail-clip assay and thrombus instability in an in vivo thrombosis model. This instability was confirmed in vitro in a whole-blood perfusion assay under blood flow conditions. Aggregations induced by thrombin and collagen were also impaired in cKO KIF5B platelets. Furthermore, P-selectin exposure, PF4 (platelet factor 4) secretion, and ATP release after thrombin stimulation were impaired in cKO KIF5B platelets, highlighting the role of kinesin-1 in α-granule and dense granule secretion. Importantly, exogenous ADP rescued normal thrombin induced-aggregation in cKO KIF5B platelets, which indicates that impaired aggregation was because of defective release of ADP and dense granules. Last, we demonstrated that kinesin-1 interacts with the molecular machinery comprising the granule-associated Rab27 protein and the Slp4 (synaptotagmin-like protein 4/SYTL4) adaptor protein. Conclusions— Our results indicate that a kinesin-1–dependent process plays a role for platelet function by acting into the mechanism underlying α-granule and dense granule secretion.
-
KIF5B modulates processing and secretion of von willebrand factor in endothelial cells and mice
Cardiovascular Pharmacology: Open Access, 2018Co-Authors: Yue Zhuo, Ke Zhang, Erhard Hofer, Jian-dong HuangAbstract:Von Willebrand factor (VWF) secreted by Weibel-Palade bodies within endothelial cells is critical to maintain normal platelet adhesion during vascular arrest. Because the transportation of VWF is microtubule-dependent partly via kinesin activity, suppression of kinesin could affect intracellular trafficking of VWF. In this study, we investigated the role of KIF5B, the key member of the kinesin superfamily, in the processing and secretion of VWF. A hypothetical interaction between VWF and KIF5B was confirmed and the tail domain of KIF5B was identified as VWF binding region. Knocking-down KIF5B in human umbilical vein endothelial cells led to significantly increased non-stimulated VWF secretion, considerably higher ratio of pro-VWF to mature VWF, and shorter VWF length. Consistent to the in vitro assay, KIF5B knockdown mice demonstrated dramatically increased VWF secretion after epinephrine stimulation. Significantly prolonged bleeding time was observed in these KIF5B knockdown mice as well, which was further elucidated by the decreased basal/regulated VWF secretion in KIF5B knockdown mice comparing to their wild-type littermates. Taken together, these findings suggest that KIF5B modulates processing and secretion of VWF in vitro and in vivo.
-
adipose specific deletion of KIF5B exacerbates obesity and insulin resistance in a mouse model of diet induced obesity
The FASEB Journal, 2017Co-Authors: Jing Pang, Jian-dong Huang, Ping Jiang, Huan Gong, Zai Wang, Jian Li, Zhenhe Wang, Yunxuan Li, Jin Li, Tiemei ZhangAbstract:Recent studies have shown that KIF5B (conventional kinesin heavy chain) mediates glucose transporter type 4 translocation and adiponectin secretion in 3T3-L1 adipocytes, suggesting an involvement o...
Hidefumi Sasaki - One of the best experts on this subject based on the ideXlab platform.
-
KIF5B ret fusion gene in surgically treated adenocarcinoma of the lung
Oncology Reports, 2012Co-Authors: Keisuke Yokota, Hidefumi Sasaki, Katsuhiro Okuda, Shigeki Shimizu, Masayuki Shitara, Yuu Hikosaka, Satoru Moriyama, Motoki Yano, Yoshitaka FujiiAbstract:: Recently, a novel fusion gene resulting from a linkage between the kinesin family member 5B gene (KIF5B; 10p11.22) and the rearranged during transfection gene (RET; 10q11.21) was identified in non-small cell lung cancer (NSCLC). However, the correlation between the KIF5B/RET fusion gene status and the clinicopathological features of surgically-treated lung cancer has not been well characterized. In this study, we have independently investigated the KIF5B/RET fusion gene status in 371 surgically-treated NSCLCs (270 were adenocarcinomas and 101 were squamous cell carcinomas), 60 breast cancers, 11 metastatic lung cancers from colon cancers and thyroid papillary adenocarcinoma cases at the Nagoya City University Hospital. The fusion gene status was analyzed by an RT-PCR-based assay and by using direct sequencing. We detected 3 of 270 cases of KIF5B/RET fusion genes in adenocarcinomas (1.1%) consisting of female and never smokers with mixed subtype adenocarcinomas. The fusion genes were detected exclusively with other mutations, such as EGFR, Kras, Braf, erbB2 mutations, and EML4/ALK fusion. KIF5B/RET fusion was not detected in the cases with squamous cell carcinoma or other types of cancers. From the 3 cases, 2 were KIF5B (exon 15); RET (exon 12) fusions with papillary dominant and 1 case was KIF5B (exon 22); RET (exon 12) fusion with solid dominant adenocarcinoma. The matched normal lung tissues did not display translocation. We reported KIF5B/RET fusion genes as a driver somatic mutation of lung adenocarcinomas. The cinicopathological backgrounds of the KIF5B/RET fusion-positive patients were similar with those of the EML4/ALK fusion-positive patients. The chimeric oncogene may be a promising molecular target for the personalized diagnosis and treatment of NSCLC.
-
ret expression and detection of KIF5B ret gene rearrangements in japanese lung cancer
Cancer Medicine, 2012Co-Authors: Hidefumi Sasaki, Keisuke Yokota, Katsuhiro Okuda, Shigeki Shimizu, Masayuki Shitara, Satoru Moriyama, Yoichi Tani, Masahiko Maekawa, Yu Hikosaka, Motoki YanoAbstract:RET encodes the tyrosine kinase receptor of growth factors belonging to the glial-derived neurotrophic factor family. Recently, RET gene rearrangements with N-terminal of KIF5B gene were identified in lung adenocarcinomas from large-scale sequencing. We investigated RET mRNA expression by real-time reverse-transcriptase polymerase chain reaction (RT-PCR) assay using LightCycler, and KIF5B/RET gene rearrangements using newly established fluorescence in situ hybridization (FISH) analysis in surgically treated nonsmall cell lung cancer (NSCLC) cases. RET protein expression was also investigated by immunohistochemistry (IHC). This study included 157 surgically removed NSCLC cases for mRNA level analyses. The RET/β actin mRNA levels were not significantly different between lung cancer (6.359 ± 15.268) and adjacent normal lung tissues (8.205 ± 28.931, P = 0.6332). Tumor/normal (T/N) ratio of RET/β actin mRNA levels was not different within gender, stage, smoking status, and pathological subtypes. T/N ratio of RET/β actin mRNA levels was significantly higher in KIF5B/RET rearrangement samples (161.763 ± 123.488) than in wild-type samples (5.9013 ± 17.148, P = 0.044). Although RET IHC positivity was not perfectly correlated with KIF5B/RET arrangement, we have detected the KIF5B/RET rearrangements using FISH analysis. Thus, we have successfully introduced FISH for diagnosing KIF5B/RET positive lung adenocarcinoma. This method facilitates the molecular evaluation for RET fusions and could be applicable in clinical practice to detect lung cancer that may be responsive to RET inhibitors.
-
KIF5B/RET fusion gene in surgically-treated adenocarcinoma of the lung.
Oncology Reports, 2012Co-Authors: Keisuke Yokota, Hidefumi Sasaki, Katsuhiro Okuda, Shigeki Shimizu, Masayuki Shitara, Yuu Hikosaka, Satoru Moriyama, Motoki Yano, Yoshitaka FujiiAbstract:: Recently, a novel fusion gene resulting from a linkage between the kinesin family member 5B gene (KIF5B; 10p11.22) and the rearranged during transfection gene (RET; 10q11.21) was identified in non-small cell lung cancer (NSCLC). However, the correlation between the KIF5B/RET fusion gene status and the clinicopathological features of surgically-treated lung cancer has not been well characterized. In this study, we have independently investigated the KIF5B/RET fusion gene status in 371 surgically-treated NSCLCs (270 were adenocarcinomas and 101 were squamous cell carcinomas), 60 breast cancers, 11 metastatic lung cancers from colon cancers and thyroid papillary adenocarcinoma cases at the Nagoya City University Hospital. The fusion gene status was analyzed by an RT-PCR-based assay and by using direct sequencing. We detected 3 of 270 cases of KIF5B/RET fusion genes in adenocarcinomas (1.1%) consisting of female and never smokers with mixed subtype adenocarcinomas. The fusion genes were detected exclusively with other mutations, such as EGFR, Kras, Braf, erbB2 mutations, and EML4/ALK fusion. KIF5B/RET fusion was not detected in the cases with squamous cell carcinoma or other types of cancers. From the 3 cases, 2 were KIF5B (exon 15); RET (exon 12) fusions with papillary dominant and 1 case was KIF5B (exon 22); RET (exon 12) fusion with solid dominant adenocarcinoma. The matched normal lung tissues did not display translocation. We reported KIF5B/RET fusion genes as a driver somatic mutation of lung adenocarcinomas. The cinicopathological backgrounds of the KIF5B/RET fusion-positive patients were similar with those of the EML4/ALK fusion-positive patients. The chimeric oncogene may be a promising molecular target for the personalized diagnosis and treatment of NSCLC.
-
RET expression and detection of KIF5B/RET gene rearrangements in Japanese lung cancer
Cancer Medicine, 2012Co-Authors: Hidefumi Sasaki, Keisuke Yokota, Katsuhiro Okuda, Shigeki Shimizu, Masayuki Shitara, Satoru Moriyama, Yoichi Tani, Masahiko Maekawa, Yu Hikosaka, Motoki YanoAbstract:RET encodes the tyrosine kinase receptor of growth factors belonging to the glial-derived neurotrophic factor family. Recently, RET gene rearrangements with N-terminal of KIF5B gene were identified in lung adenocarcinomas from large-scale sequencing. We investigated RET mRNA expression by real-time reverse-transcriptase polymerase chain reaction (RT-PCR) assay using LightCycler, and KIF5B/RET gene rearrangements using newly established fluorescence in situ hybridization (FISH) analysis in surgically treated nonsmall cell lung cancer (NSCLC) cases. RET protein expression was also investigated by immunohistochemistry (IHC). This study included 157 surgically removed NSCLC cases for mRNA level analyses. The RET/β actin mRNA levels were not significantly different between lung cancer (6.359 ± 15.268) and adjacent normal lung tissues (8.205 ± 28.931, P = 0.6332). Tumor/normal (T/N) ratio of RET/β actin mRNA levels was not different within gender, stage, smoking status, and pathological subtypes. T/N ratio of RET/β actin mRNA levels was significantly higher in KIF5B/RET rearrangement samples (161.763 ± 123.488) than in wild-type samples (5.9013 ± 17.148, P = 0.044). Although RET IHC positivity was not perfectly correlated with KIF5B/RET arrangement, we have detected the KIF5B/RET rearrangements using FISH analysis. Thus, we have successfully introduced FISH for diagnosing KIF5B/RET positive lung adenocarcinoma. This method facilitates the molecular evaluation for RET fusions and could be applicable in clinical practice to detect lung cancer that may be responsive to RET inhibitors.
-
abstract lb 88 identification of recurrent oncogenic KIF5B ret rearrangements in non small cell lung cancer
Cancer Research, 2012Co-Authors: Marzia Capelletti, Hidefumi Sasaki, Doron Lipson, Geoff Otto, Roman Yelensky, Dalia Ercan, Seungil Park, Jeffrey S Ross, Philip J Stephens, Maureen T CroninAbstract:Proceedings: AACR 103rd Annual Meeting 2012‐‐ Mar 31‐Apr 4, 2012; Chicago, IL Background: A large number of non-small cell lung cancer (NSCLC) cases from never/former light smokers can be explained by driving oncogenic alterations in EGFR, KRAS, ERBB2, BRAF, ALK and ROS1. EGFR and ALK targeted tyrosine kinase inhibitors are effective clinical therapies for EGFR mutant and ALK rearranged NSCLC, respectively. We wished to study cancers that do not harbor a known genomic alteration in order to identify novel therapeutic targets that may increase treatment options for NSCLC patients. Methods and Results: We initially sequenced a NSCLC specimen from a 44 year old Caucasian never smoker in a CLIA certified lab (Foundation Medicine) using a next generation sequencing assay that captures and sequences 2574 coding exons representing 145 cancer relevant genes plus 37 introns from 14 genes frequently rearranged in cancer. We identified an 11,294,741 bp pericentric inversion on chromosome 10 generating a novel gene fusion joining exons 1-15 of KIF5B to exons 12-20 of RET (K15:R12). This fusion gene contains the kinesin motor and coiled-coil domains of KIF5B and the entire tyrosine kinase domain of RET. Expression of RET was confirmed by immunohistochemistry (IHC) and cDNA sequencing detected a 7.3-fold RET expression increase beginning at exon 12 relative to exons 1-11. Screening of additional 117 NSCLC patients using RET IHC identified 22 positive cases; sequencing of 15/22 of these identified 1 additional patient with a KIF5B-RET fusion. We also evaluated 526 tumors from never/former limited smokers (121 Caucasian and 405 Asian) and identified 10 additional (1/121 Caucasian (0.8%) and 9/405 Asian (2%)) positive patients. All fusion positive tumors were wild type for known oncogenes (frequency of 6.3 % (10/159) in WT patients). Four unique KIF5B-RET variants were identified: 8 K15:R12 (variant 1), 3 K16:R12 (variant 2), 1 K22:R12 (variant 3) and 1 K15:R11 (variant 4). We introduced K15:R12 (variant 1) into Ba/F3 cells and observed IL-3 independent growth consistent with oncogenic transformation. These KIF5B-RET Ba/F3 cells were sensitive to sunitinib, sorafenib and vandetinib, multi-targeted kinase inhibitors that inhibit RET, but not gefitinib, an EGFR kinase inhibitor. Sunitinib, but not gefitinib, inhibited RET phosphorylation in the KIF5B-RET Ba/F3 cells. Conclusions: We identify a novel oncogenic KIF5B-RET fusion gene in a subset of NSCLC patients lacking other known driver mutations. Our findings suggest that RET kinase inhibitors should be tested in prospective clinical trials for therapeutic benefit in NSCLC patients bearing KIF5B-RET rearrangements. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr LB-88. doi:1538-7445.AM2012-LB-88
Zai Wang - One of the best experts on this subject based on the ideXlab platform.
-
adipose specific deletion of KIF5B exacerbates obesity and insulin resistance in a mouse model of diet induced obesity
The FASEB Journal, 2017Co-Authors: Jing Pang, Jian-dong Huang, Ping Jiang, Huan Gong, Zai Wang, Jian Li, Zhenhe Wang, Yunxuan Li, Jin Li, Tiemei ZhangAbstract:Recent studies have shown that KIF5B (conventional kinesin heavy chain) mediates glucose transporter type 4 translocation and adiponectin secretion in 3T3-L1 adipocytes, suggesting an involvement o...
-
conventional kinesin KIF5B mediates adiponectin secretion in 3t3 l1 adipocytes
Biochemical and Biophysical Research Communications, 2016Co-Authors: Jing Pang, Jian-dong Huang, Ping Jiang, Huan Gong, Zai Wang, Jian Li, Tiemei ZhangAbstract:Insulin stimulates adiponectin secretion and glucose transporter type 4 (GLUT4) translocation in adipocyte to regulate metabolism homeostasis. Similar to GLUT4 translocation, intracellular trafficking and release of adiponectin in adipocytes relies on the trans-Golgi network and endosomal system. Recent studies show that the heavy chain of conventional kinesin (KIF5B) mediates GLUT4 translocation in murine 3T3-L1 adipocytes, however, the motor machinery involved in mediating intracellular trafficking and release of adiponectin is unknown. Here, we examined the role of KIF5B in the regulation of adiponectin secretion. The KIF5B level was up-regulated during 3T3-L1 adipogenesis. This increase in cytosolic KIF5B was synchronized with the induction of adiponectin. Endogenous KIF5B and adiponectin were partially colocalized at the peri-nuclear and cytosolic regions. In addition, adiponectin-containing vesicles were co-immunoprecipitated with KIF5B. Knockdown of KIF5B resulted in a marked inhibition of adiponectin secretion and overexpression of KIF5B enhanced adiponectin release, whereas leptin secretion was not affected by changes in KIF5B expression. These data suggest that the secretion of adiponectin, but not leptin, is dependent on functional KIF5B.
-
stable knockdown of KIF5B in mdck cells leads to epithelial mesenchymal transition
Biochemical and Biophysical Research Communications, 2015Co-Authors: Bin Yu, Zai Wang, Jian-dong HuangAbstract:Polarization of epithelial cells requires vectorial sorting and transport of polarity proteins to apical or basolateral domains. KIF5B is the mouse homologue of the human ubiquitous Kinesin Heavy Chain (uKHC). To investigate the function of KIF5B in epithelial cells, we examined the phenotypes of KIF5B-deficient MDCK cells. Stable knockdown of KIF5B in MDCK cells resulted in reduced cell proliferation rate, profound changes in cell morphology, loss of epithelial cell marker, and gain of mesenchymal marker, as well as increased cell migration, invasion, and tumorigenesis abilities. E-cadherin and NMMIIA could interact with KIF5B in polarized MDCK cells, and their expression levels were decreased in KIF5B-deficient MDCK cells. Overexpression of E-cadherin and NMMIIA in KIF5B depleted MDCK cells could decrease mesenchymal marker expression and cell migration ability. These results indicate that stable knockdown of KIF5B in MDCK cells can lead to epithelial–mesenchymal transition, which is mediated by defective E-cadherin and NMMIIA expression.
-
Stable knockdown of KIF5B in MDCK cells leads to epithelial–mesenchymal transition
Biochemical and Biophysical Research Communications, 2015Co-Authors: Bin Yu, Zai Wang, Jian-dong HuangAbstract:Polarization of epithelial cells requires vectorial sorting and transport of polarity proteins to apical or basolateral domains. KIF5B is the mouse homologue of the human ubiquitous Kinesin Heavy Chain (uKHC). To investigate the function of KIF5B in epithelial cells, we examined the phenotypes of KIF5B-deficient MDCK cells. Stable knockdown of KIF5B in MDCK cells resulted in reduced cell proliferation rate, profound changes in cell morphology, loss of epithelial cell marker, and gain of mesenchymal marker, as well as increased cell migration, invasion, and tumorigenesis abilities. E-cadherin and NMMIIA could interact with KIF5B in polarized MDCK cells, and their expression levels were decreased in KIF5B-deficient MDCK cells. Overexpression of E-cadherin and NMMIIA in KIF5B depleted MDCK cells could decrease mesenchymal marker expression and cell migration ability. These results indicate that stable knockdown of KIF5B in MDCK cells can lead to epithelial–mesenchymal transition, which is mediated by defective E-cadherin and NMMIIA expression.
-
analysis of KIF5B expression during mouse kidney development
PLOS ONE, 2015Co-Authors: Xiuling Li, Zai Wang, Zhigang Duan, Song Lu, Jian-dong HuangAbstract:Recent studies showed that kidney-specific inactivation of Kif3a produces kidney cysts and renal failure, suggesting that kinesin-mediated intracellular transportation is important for the establishement and maintenance of renal epithelial cell polarity and normal nephron functions. KIF5B, one of the most conserved kinesin heavy chain, is the mouse homologue of the human ubiquitous Kinesin Heavy Chain (uKHC). In order to elucidate the role of KIF5B in kidney development and function, it is essential to establish its expression profile within the organ. Therefore, in this study, we examined the expression pattern of KIF5B in mouse kidney. Kidneys from embryonic (E) 12.5-, 16.5-dpc (days post coitus) mouse fetuses, from postnatal (P) day 0, 10, 20 pups and from adult mice were collected. The distribution of KIF5B was analyzed by immunostaining. The possible involvement of KIF5B in kidney development was investigated in conditional mutant mice by using a Cre-LoxP strategy. This study showed that the distribution of KIF5B displayed spatiotemporal changes during postnatal kidney development. In kidneys of new born mice, KIF5B was strongly expressed in all developing tubules and in the ureteric bud, but not in the glomerulus or in other early-developing structures, such as the cap mesenchyme, the comma-shaped body, and the S-shaped body. In kidneys of postnatal day 20 or of older mice, however, KIF5B was localized selectively in the basolateral domain of epithelial cells of the thick ascending loop of Henle, as well as of the distal convoluted tubule, with little expression being observed in the proximal tubule or in the collecting duct. Conditional knock-down of KIF5B in mouse kidney did not result in detectable morphological defects, but it did lead to a decrease in cell proliferation rate and also to a mislocalization of Na+/K+/-ATPase, indicating that although KIF5B is non-essential for kidney morphogenesis, it is important for nephron maturation.
Keisuke Yokota - One of the best experts on this subject based on the ideXlab platform.
-
KIF5B ret fusion gene in surgically treated adenocarcinoma of the lung
Oncology Reports, 2012Co-Authors: Keisuke Yokota, Hidefumi Sasaki, Katsuhiro Okuda, Shigeki Shimizu, Masayuki Shitara, Yuu Hikosaka, Satoru Moriyama, Motoki Yano, Yoshitaka FujiiAbstract:: Recently, a novel fusion gene resulting from a linkage between the kinesin family member 5B gene (KIF5B; 10p11.22) and the rearranged during transfection gene (RET; 10q11.21) was identified in non-small cell lung cancer (NSCLC). However, the correlation between the KIF5B/RET fusion gene status and the clinicopathological features of surgically-treated lung cancer has not been well characterized. In this study, we have independently investigated the KIF5B/RET fusion gene status in 371 surgically-treated NSCLCs (270 were adenocarcinomas and 101 were squamous cell carcinomas), 60 breast cancers, 11 metastatic lung cancers from colon cancers and thyroid papillary adenocarcinoma cases at the Nagoya City University Hospital. The fusion gene status was analyzed by an RT-PCR-based assay and by using direct sequencing. We detected 3 of 270 cases of KIF5B/RET fusion genes in adenocarcinomas (1.1%) consisting of female and never smokers with mixed subtype adenocarcinomas. The fusion genes were detected exclusively with other mutations, such as EGFR, Kras, Braf, erbB2 mutations, and EML4/ALK fusion. KIF5B/RET fusion was not detected in the cases with squamous cell carcinoma or other types of cancers. From the 3 cases, 2 were KIF5B (exon 15); RET (exon 12) fusions with papillary dominant and 1 case was KIF5B (exon 22); RET (exon 12) fusion with solid dominant adenocarcinoma. The matched normal lung tissues did not display translocation. We reported KIF5B/RET fusion genes as a driver somatic mutation of lung adenocarcinomas. The cinicopathological backgrounds of the KIF5B/RET fusion-positive patients were similar with those of the EML4/ALK fusion-positive patients. The chimeric oncogene may be a promising molecular target for the personalized diagnosis and treatment of NSCLC.
-
ret expression and detection of KIF5B ret gene rearrangements in japanese lung cancer
Cancer Medicine, 2012Co-Authors: Hidefumi Sasaki, Keisuke Yokota, Katsuhiro Okuda, Shigeki Shimizu, Masayuki Shitara, Satoru Moriyama, Yoichi Tani, Masahiko Maekawa, Yu Hikosaka, Motoki YanoAbstract:RET encodes the tyrosine kinase receptor of growth factors belonging to the glial-derived neurotrophic factor family. Recently, RET gene rearrangements with N-terminal of KIF5B gene were identified in lung adenocarcinomas from large-scale sequencing. We investigated RET mRNA expression by real-time reverse-transcriptase polymerase chain reaction (RT-PCR) assay using LightCycler, and KIF5B/RET gene rearrangements using newly established fluorescence in situ hybridization (FISH) analysis in surgically treated nonsmall cell lung cancer (NSCLC) cases. RET protein expression was also investigated by immunohistochemistry (IHC). This study included 157 surgically removed NSCLC cases for mRNA level analyses. The RET/β actin mRNA levels were not significantly different between lung cancer (6.359 ± 15.268) and adjacent normal lung tissues (8.205 ± 28.931, P = 0.6332). Tumor/normal (T/N) ratio of RET/β actin mRNA levels was not different within gender, stage, smoking status, and pathological subtypes. T/N ratio of RET/β actin mRNA levels was significantly higher in KIF5B/RET rearrangement samples (161.763 ± 123.488) than in wild-type samples (5.9013 ± 17.148, P = 0.044). Although RET IHC positivity was not perfectly correlated with KIF5B/RET arrangement, we have detected the KIF5B/RET rearrangements using FISH analysis. Thus, we have successfully introduced FISH for diagnosing KIF5B/RET positive lung adenocarcinoma. This method facilitates the molecular evaluation for RET fusions and could be applicable in clinical practice to detect lung cancer that may be responsive to RET inhibitors.
-
KIF5B/RET fusion gene in surgically-treated adenocarcinoma of the lung.
Oncology Reports, 2012Co-Authors: Keisuke Yokota, Hidefumi Sasaki, Katsuhiro Okuda, Shigeki Shimizu, Masayuki Shitara, Yuu Hikosaka, Satoru Moriyama, Motoki Yano, Yoshitaka FujiiAbstract:: Recently, a novel fusion gene resulting from a linkage between the kinesin family member 5B gene (KIF5B; 10p11.22) and the rearranged during transfection gene (RET; 10q11.21) was identified in non-small cell lung cancer (NSCLC). However, the correlation between the KIF5B/RET fusion gene status and the clinicopathological features of surgically-treated lung cancer has not been well characterized. In this study, we have independently investigated the KIF5B/RET fusion gene status in 371 surgically-treated NSCLCs (270 were adenocarcinomas and 101 were squamous cell carcinomas), 60 breast cancers, 11 metastatic lung cancers from colon cancers and thyroid papillary adenocarcinoma cases at the Nagoya City University Hospital. The fusion gene status was analyzed by an RT-PCR-based assay and by using direct sequencing. We detected 3 of 270 cases of KIF5B/RET fusion genes in adenocarcinomas (1.1%) consisting of female and never smokers with mixed subtype adenocarcinomas. The fusion genes were detected exclusively with other mutations, such as EGFR, Kras, Braf, erbB2 mutations, and EML4/ALK fusion. KIF5B/RET fusion was not detected in the cases with squamous cell carcinoma or other types of cancers. From the 3 cases, 2 were KIF5B (exon 15); RET (exon 12) fusions with papillary dominant and 1 case was KIF5B (exon 22); RET (exon 12) fusion with solid dominant adenocarcinoma. The matched normal lung tissues did not display translocation. We reported KIF5B/RET fusion genes as a driver somatic mutation of lung adenocarcinomas. The cinicopathological backgrounds of the KIF5B/RET fusion-positive patients were similar with those of the EML4/ALK fusion-positive patients. The chimeric oncogene may be a promising molecular target for the personalized diagnosis and treatment of NSCLC.
-
RET expression and detection of KIF5B/RET gene rearrangements in Japanese lung cancer
Cancer Medicine, 2012Co-Authors: Hidefumi Sasaki, Keisuke Yokota, Katsuhiro Okuda, Shigeki Shimizu, Masayuki Shitara, Satoru Moriyama, Yoichi Tani, Masahiko Maekawa, Yu Hikosaka, Motoki YanoAbstract:RET encodes the tyrosine kinase receptor of growth factors belonging to the glial-derived neurotrophic factor family. Recently, RET gene rearrangements with N-terminal of KIF5B gene were identified in lung adenocarcinomas from large-scale sequencing. We investigated RET mRNA expression by real-time reverse-transcriptase polymerase chain reaction (RT-PCR) assay using LightCycler, and KIF5B/RET gene rearrangements using newly established fluorescence in situ hybridization (FISH) analysis in surgically treated nonsmall cell lung cancer (NSCLC) cases. RET protein expression was also investigated by immunohistochemistry (IHC). This study included 157 surgically removed NSCLC cases for mRNA level analyses. The RET/β actin mRNA levels were not significantly different between lung cancer (6.359 ± 15.268) and adjacent normal lung tissues (8.205 ± 28.931, P = 0.6332). Tumor/normal (T/N) ratio of RET/β actin mRNA levels was not different within gender, stage, smoking status, and pathological subtypes. T/N ratio of RET/β actin mRNA levels was significantly higher in KIF5B/RET rearrangement samples (161.763 ± 123.488) than in wild-type samples (5.9013 ± 17.148, P = 0.044). Although RET IHC positivity was not perfectly correlated with KIF5B/RET arrangement, we have detected the KIF5B/RET rearrangements using FISH analysis. Thus, we have successfully introduced FISH for diagnosing KIF5B/RET positive lung adenocarcinoma. This method facilitates the molecular evaluation for RET fusions and could be applicable in clinical practice to detect lung cancer that may be responsive to RET inhibitors.
Motoki Yano - One of the best experts on this subject based on the ideXlab platform.
-
KIF5B ret fusion gene in surgically treated adenocarcinoma of the lung
Oncology Reports, 2012Co-Authors: Keisuke Yokota, Hidefumi Sasaki, Katsuhiro Okuda, Shigeki Shimizu, Masayuki Shitara, Yuu Hikosaka, Satoru Moriyama, Motoki Yano, Yoshitaka FujiiAbstract:: Recently, a novel fusion gene resulting from a linkage between the kinesin family member 5B gene (KIF5B; 10p11.22) and the rearranged during transfection gene (RET; 10q11.21) was identified in non-small cell lung cancer (NSCLC). However, the correlation between the KIF5B/RET fusion gene status and the clinicopathological features of surgically-treated lung cancer has not been well characterized. In this study, we have independently investigated the KIF5B/RET fusion gene status in 371 surgically-treated NSCLCs (270 were adenocarcinomas and 101 were squamous cell carcinomas), 60 breast cancers, 11 metastatic lung cancers from colon cancers and thyroid papillary adenocarcinoma cases at the Nagoya City University Hospital. The fusion gene status was analyzed by an RT-PCR-based assay and by using direct sequencing. We detected 3 of 270 cases of KIF5B/RET fusion genes in adenocarcinomas (1.1%) consisting of female and never smokers with mixed subtype adenocarcinomas. The fusion genes were detected exclusively with other mutations, such as EGFR, Kras, Braf, erbB2 mutations, and EML4/ALK fusion. KIF5B/RET fusion was not detected in the cases with squamous cell carcinoma or other types of cancers. From the 3 cases, 2 were KIF5B (exon 15); RET (exon 12) fusions with papillary dominant and 1 case was KIF5B (exon 22); RET (exon 12) fusion with solid dominant adenocarcinoma. The matched normal lung tissues did not display translocation. We reported KIF5B/RET fusion genes as a driver somatic mutation of lung adenocarcinomas. The cinicopathological backgrounds of the KIF5B/RET fusion-positive patients were similar with those of the EML4/ALK fusion-positive patients. The chimeric oncogene may be a promising molecular target for the personalized diagnosis and treatment of NSCLC.
-
ret expression and detection of KIF5B ret gene rearrangements in japanese lung cancer
Cancer Medicine, 2012Co-Authors: Hidefumi Sasaki, Keisuke Yokota, Katsuhiro Okuda, Shigeki Shimizu, Masayuki Shitara, Satoru Moriyama, Yoichi Tani, Masahiko Maekawa, Yu Hikosaka, Motoki YanoAbstract:RET encodes the tyrosine kinase receptor of growth factors belonging to the glial-derived neurotrophic factor family. Recently, RET gene rearrangements with N-terminal of KIF5B gene were identified in lung adenocarcinomas from large-scale sequencing. We investigated RET mRNA expression by real-time reverse-transcriptase polymerase chain reaction (RT-PCR) assay using LightCycler, and KIF5B/RET gene rearrangements using newly established fluorescence in situ hybridization (FISH) analysis in surgically treated nonsmall cell lung cancer (NSCLC) cases. RET protein expression was also investigated by immunohistochemistry (IHC). This study included 157 surgically removed NSCLC cases for mRNA level analyses. The RET/β actin mRNA levels were not significantly different between lung cancer (6.359 ± 15.268) and adjacent normal lung tissues (8.205 ± 28.931, P = 0.6332). Tumor/normal (T/N) ratio of RET/β actin mRNA levels was not different within gender, stage, smoking status, and pathological subtypes. T/N ratio of RET/β actin mRNA levels was significantly higher in KIF5B/RET rearrangement samples (161.763 ± 123.488) than in wild-type samples (5.9013 ± 17.148, P = 0.044). Although RET IHC positivity was not perfectly correlated with KIF5B/RET arrangement, we have detected the KIF5B/RET rearrangements using FISH analysis. Thus, we have successfully introduced FISH for diagnosing KIF5B/RET positive lung adenocarcinoma. This method facilitates the molecular evaluation for RET fusions and could be applicable in clinical practice to detect lung cancer that may be responsive to RET inhibitors.
-
KIF5B/RET fusion gene in surgically-treated adenocarcinoma of the lung.
Oncology Reports, 2012Co-Authors: Keisuke Yokota, Hidefumi Sasaki, Katsuhiro Okuda, Shigeki Shimizu, Masayuki Shitara, Yuu Hikosaka, Satoru Moriyama, Motoki Yano, Yoshitaka FujiiAbstract:: Recently, a novel fusion gene resulting from a linkage between the kinesin family member 5B gene (KIF5B; 10p11.22) and the rearranged during transfection gene (RET; 10q11.21) was identified in non-small cell lung cancer (NSCLC). However, the correlation between the KIF5B/RET fusion gene status and the clinicopathological features of surgically-treated lung cancer has not been well characterized. In this study, we have independently investigated the KIF5B/RET fusion gene status in 371 surgically-treated NSCLCs (270 were adenocarcinomas and 101 were squamous cell carcinomas), 60 breast cancers, 11 metastatic lung cancers from colon cancers and thyroid papillary adenocarcinoma cases at the Nagoya City University Hospital. The fusion gene status was analyzed by an RT-PCR-based assay and by using direct sequencing. We detected 3 of 270 cases of KIF5B/RET fusion genes in adenocarcinomas (1.1%) consisting of female and never smokers with mixed subtype adenocarcinomas. The fusion genes were detected exclusively with other mutations, such as EGFR, Kras, Braf, erbB2 mutations, and EML4/ALK fusion. KIF5B/RET fusion was not detected in the cases with squamous cell carcinoma or other types of cancers. From the 3 cases, 2 were KIF5B (exon 15); RET (exon 12) fusions with papillary dominant and 1 case was KIF5B (exon 22); RET (exon 12) fusion with solid dominant adenocarcinoma. The matched normal lung tissues did not display translocation. We reported KIF5B/RET fusion genes as a driver somatic mutation of lung adenocarcinomas. The cinicopathological backgrounds of the KIF5B/RET fusion-positive patients were similar with those of the EML4/ALK fusion-positive patients. The chimeric oncogene may be a promising molecular target for the personalized diagnosis and treatment of NSCLC.
-
RET expression and detection of KIF5B/RET gene rearrangements in Japanese lung cancer
Cancer Medicine, 2012Co-Authors: Hidefumi Sasaki, Keisuke Yokota, Katsuhiro Okuda, Shigeki Shimizu, Masayuki Shitara, Satoru Moriyama, Yoichi Tani, Masahiko Maekawa, Yu Hikosaka, Motoki YanoAbstract:RET encodes the tyrosine kinase receptor of growth factors belonging to the glial-derived neurotrophic factor family. Recently, RET gene rearrangements with N-terminal of KIF5B gene were identified in lung adenocarcinomas from large-scale sequencing. We investigated RET mRNA expression by real-time reverse-transcriptase polymerase chain reaction (RT-PCR) assay using LightCycler, and KIF5B/RET gene rearrangements using newly established fluorescence in situ hybridization (FISH) analysis in surgically treated nonsmall cell lung cancer (NSCLC) cases. RET protein expression was also investigated by immunohistochemistry (IHC). This study included 157 surgically removed NSCLC cases for mRNA level analyses. The RET/β actin mRNA levels were not significantly different between lung cancer (6.359 ± 15.268) and adjacent normal lung tissues (8.205 ± 28.931, P = 0.6332). Tumor/normal (T/N) ratio of RET/β actin mRNA levels was not different within gender, stage, smoking status, and pathological subtypes. T/N ratio of RET/β actin mRNA levels was significantly higher in KIF5B/RET rearrangement samples (161.763 ± 123.488) than in wild-type samples (5.9013 ± 17.148, P = 0.044). Although RET IHC positivity was not perfectly correlated with KIF5B/RET arrangement, we have detected the KIF5B/RET rearrangements using FISH analysis. Thus, we have successfully introduced FISH for diagnosing KIF5B/RET positive lung adenocarcinoma. This method facilitates the molecular evaluation for RET fusions and could be applicable in clinical practice to detect lung cancer that may be responsive to RET inhibitors.
