The Experts below are selected from a list of 975 Experts worldwide ranked by ideXlab platform
Yalin Dong - One of the best experts on this subject based on the ideXlab platform.
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Transgelin 2 Promotes Paclitaxel Resistance, Migration, and Invasion of Breast Cancer by Directly Interacting with PTEN and Activating PI3K/Akt/GSK-3β Pathway.
Molecular Cancer Therapeutics, 2019Co-Authors: Leichao Liu, Ruifang Hao, Yang Liu, Siying Chen, Haisheng You, Ti Meng, Xiaowei Zheng, Yan Yan, Jianfeng Xing, Yalin DongAbstract:MDR and tumor migration and invasion are still the main obstacles to effective breast cancer chemotherapies. Transgelin 2 has recently been shown to induce drug resistance, tumor migration, and invasion. The aim of this study was to determine the biological functions of Transgelin 2 and the mechanism underlying how Transgelin 2 induces paclitaxel (PTX) resistance and the migration and invasion of breast cancer. We detected that the protein level of Transgelin 2 was significantly upregulated in breast cancer tissues compared with adjacent nontumor tissues. A bioinformatics analysis indicated that Transgelin 2 was significantly related to clinicopathologic parameters and patient prognosis. Overexpression of Transgelin 2 enhanced the migration and invasion of human breast cancer cells and decreased the sensitivity of breast cancer cells to paclitaxel. Meanwhile, the tumorigenesis and metastasis of breast cancer cells were also enhanced by Transgelin 2 overexpression in vivo. Moreover, Transgelin 2 overexpression activated the PI3K/Akt/GSK-3β pathway by increasing the phosphorylation levels of Akt and GSK-3β and decreasing the expression of PTEN. We also found that Transgelin 2 could directly interact with PTEN and was located upstream of PTEN. Furthermore, the PI3K/Akt pathway inhibitor MK-2206 reversed the resistance to paclitaxel and inhibited the migration and invasion of breast cancer cells. These findings indicate that Transgelin 2 promotes paclitaxel resistance and the migration and invasion of breast cancer by directly interacting with PTEN and activating the PI3K/Akt/GSK-3β pathway. Transgelin 2 may therefore be useful as a novel biomarker and therapeutic target for breast cancer.
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Transgelin 2 expression in breast cancer and its relationships with clinicopathological features and patient outcome
Breast Cancer, 2019Co-Authors: Ruifang Hao, Yang Liu, Leichao Liu, Siying Chen, Haisheng You, Yalin DongAbstract:Transgelin-2 is an actin-binding protein that is widely expressed in various tissues and organs of the body, and reportedly may participate in the development and progression of multiple cancers. However, the clinical significance of Transgelin-2 still remains controversial. We, therefore, aimed to determine the expression of Transgelin-2 in breast cancer as well as its correlation with the tumorigenesis, progression and prognosis of human breast cancer. We collected tissues of 58 breast cancer patients from our hospital and 1090 samples from The Cancer Genome Atlas (TCGA) database. X-tile software was used to divide the Transgelin-2 mRNA expression level in the database, logistic regression model was used to identify independent factors influencing Transgelin-2 mRNA expression, and then Cox regression and Kaplan–Meier analysis were used to find factors that influence survival of breast cancer. Transgelin-2 was significantly overexpressed in breast cancer tissues from our hospital and receiver operating characteristic (ROC) curve indicated that Transgelin-2 may have diagnostic value. Meanwhile, estrogen receptor (ER) was in inverse correlation with Transgelin-2 protein and mRNA expression, and Transgelin-2 expression was positively correlated with Ki67 in breast cancer tissues. Logistic regression model revealed that TNM stage, ER and progesterone receptor (PR) status were independent factors for Transgelin-2 mRNA expression. Patients with high Transgelin-2 mRNA expression showed a poor survival and the trend was statistically significant only in ER-negative patients. Transgelin-2 was expressed significantly higher in breast cancer cells and correlated with some clinicopathological factors. High Transgelin-2 expression might predict poor prognosis for ER-negative patients.
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Transgelin-2: A potential oncogenic factor.
Tumor Biology, 2017Co-Authors: Ti Meng, Ruifang Hao, Leichao Liu, Siying Chen, Yalin DongAbstract:Actin-binding proteins are proteins that could bind to actin or actin fibers. As a member of actin-binding proteins, Transgelin-2 is expressed in smooth muscle cells and non-smooth muscle cells, an...
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salvianolic acid a reverses the paclitaxel resistance and inhibits the migration and invasion abilities of human breast cancer cells by inactivating Transgelin 2
Cancer Biology & Therapy, 2015Co-Authors: Xiaowei Zheng, Siying Chen, Haisheng You, Jianfeng Xing, Jiangxia Cai, Weipeng Zhang, Qianting Yang, Yalin DongAbstract:Multidrug resistance and tumor migration and invasion are the major obstacles to effective breast cancer chemotherapy, but the underlying molecular mechanisms remain unclear. This study investigated the potential of Transgelin 2 and salvianolic acid A to modulate the resistance and the migration and invasion abilities of paclitaxel-resistant human breast cancer cells (MCF-7/PTX). MCF-7/PTX cells were found to exhibit not only a high degree of resistance to paclitaxel, but also strong migration and invasion abilities. Small interfering RNA-mediated knockdown of TAGLN2 sensitized the MCF-7/PTX cells to paclitaxel, and inhibited their migration and invasion abilities. In addition, we also observed that combined salvianolic acid A and paclitaxel treatment could reverse paclitaxel resistance, markedly inhibit tumor migration and invasion, and suppress the expression of Transgelin 2 in MCF-7/PTX cells. These findings indicate that salvianolic acid A can reverse the paclitaxel resistance and inhibit the migration and invasion abilities of human breast cancer cells by down-regulating the expression of Transgelin 2, and hence could be useful in breast cancer treatments.
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Salvianolic acid A reverses paclitaxel resistance in human breast cancer MCF-7 cells via targeting the expression of Transgelin 2 and attenuating PI3 K/Akt pathway
Phytomedicine, 2014Co-Authors: Jiangxia Cai, Siying Chen, Xiaowei Zheng, Jianfeng Xing, Weipeng Zhang, Chengsen Pang, Yalin DongAbstract:Chemotherapy resistance represents a major problem for the treatment of patients with breast cancer and greatly restricts the use of first-line chemotherapeutics paclitaxel. The purpose of this study was to investigate the role of Transgelin 2 in human breast cancer paclitaxel resistance cell line (MCF-7/PTX) and the reversal mechanism of salvianolic acid A (SAA), a phenolic active compound extracted from Salvia miltiorrhiza. Western blotting and real-time quantitative polymerase chain reaction (qRT-PCR) indicated that Transgelin 2 may mediate paclitaxel resistance by activating the phosphatidylinositol 3-kinase (PI3 K)/Akt signaling pathway to suppress MCF-7/PTX cells apoptosis. The reversal ability of SAA was confirmed by MTT assay and flow cytometry, with a superior 9.1-fold reversal index and enhancement of the apoptotic cytotoxicity induced by paclitaxel. In addition, SAA effectively prevented Transgelin 2 and adenosine-triphosphate binding cassette transporter (ABC transporter) including P-glycoprotein (P-gp), multidrug resistance associated protein 1 (MRP1), and breast cancer resistance protein (BCRP) up-regulation and exhibited inhibitory effect on PI3 K/Akt signaling pathway in MCF-7/PTX cells. Taken together, SAA can reverse paclitaxel resistance through suppressing Transgelin 2 expression by mechanisms involving attenuation of PI3 K/Akt pathway activation and ABC transporter up-regulation. These results not only provide insight into the potential application of SAA in reversing paclitaxel resistance, thus facilitating the sensitivity of breast cancer chemotherapy, but also highlight a potential role of Transgelin 2 in the development of paclitaxel resistance in breast cancer.
Ying Lin - One of the best experts on this subject based on the ideXlab platform.
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elevated Transgelin tns1 expression is a potential biomarker in human colorectal cancer
Oncotarget, 2018Co-Authors: Huimin Zhou, Yiming Zhang, Wenrui Xie, Yu Yuan, Yu Chen, Ying LinAbstract:Transgelin is an actin-binding protein that regulates cell motility and other important cellular functions. Previous studies have suggested that Transgelin expression is associated with cancer development and progression, but its specific role in colorectal cancer (CRC) remains controversial. We analyzed expression of Transgelin and its candidate downstream target, tensin 1 (TNS1), in CRC patients using the ONCOMINE, Protein Atlas, and OncoLnc databases. Transgelin and TNS1 mRNA and protein levels were higher in CRC patients and CRC cell lines than in normal tissues and cells. Survival analyses using the OncoLnc database revealed that elevated TAGLN/TNS1 levels were associated with a poor overall survival in CRC patients. Transgelin suppression using siRNA decreased TNS1 expression in CRC cells, demonstrating that Transgelin induces the TNS1 expression. Importantly, suppression of Transgelin or TNS1 using siRNA decreased proliferation and invasiveness of CRC cells. These results suggest that Transgelin/TNS1 signaling promotes CRC cell proliferation and invasion, and that Transgelin/TNS1 expression levels could potentially serve as a prognostic and therapeutic target in CRC patients.
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akt and jnk signaling pathways increase the metastatic potential of colorectal cancer cells by altering Transgelin expression
Digestive Diseases and Sciences, 2016Co-Authors: Huimin Zhou, Yiming Zhang, Qi Kui Chen, Ying LinAbstract:Transgelin (SM22) plays a crucial role in colorectal cancer (CRC) progression; nevertheless, its upstream regulatory mechanisms are poorly defined. AKT and JNK signaling pathways are strongly associated with tumor progression and metastasis, and there are some indications that these pathways might be involved in Transgelin regulation. To examine the role of AKT and JNK signaling in Transgelin regulation in colorectal cancer progression. Phospho-AKT (P-AKT), phospho-JNK (P-JNK), and Transgelin expression were examined in one normal colon cell line (FHC) and three CRC cell lines (SW620, LoVo, and RKO) as well as in normal colon and CRC tissue samples by Western blot and qRT-PCR. Next, siRNA silencing of AKT or JNK pathways in SW620 cells was performed to examine their role in Transgelin regulation. The effects of siRNA silencing on SW620 cell mobility and metastatic properties were examined by cell migration, invasion assays, and actin cytoskeleton. Transgelin, P-AKT, and P-JNK were increased in all examined cell lines. Moreover, Transgelin mRNA and protein expression was especially elevated in SW620 cells. Furthermore, inhibition of Akt or JNK signaling resulted in Transgelin downregulation. When Transgelin, Akt, or JNK signaling was inhibited, SW620 cell migration and invasion were dramatically decreased with inhibition of actin cytoskeleton dynamics. This study demonstrates, for the first time, that activated AKT and JNK signaling pathways promote the overexpression of Transgelin, which potentially contributes to CRC progression and metastasis.
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P-0193 Transgelin Promotes The Invasiveness of Human Colon Cancer Cells in Vitro
Annals of Oncology, 2012Co-Authors: Ying Lin, Yuan-yuan Fang, Zhou Hui-min, Qi Kui ChenAbstract:ABSTRACT Introduction Transgelin was the top-ranked marker of metastatic potential identified in the comparison of node-positive colorectal cancer (CRC) versus node-negative CRC in our previous study1. Transgelin is localized in the nucleus of cultured CRC cells and microRNA-mediated knockdown of TAGLN (the gene encoding Transgelin) expression modulates the expression of genes involved in the epithelial-to-mesenchymal transition1. This study was initiated to investigate the hallmarks of metastasis in human colon cancer cell line RKO with stable expression of TAGLN in vitro. We also aimed to identify the downstream targets of Transgelin in RKO cells. Methods The plasmid containing human TAGLN was generated using pcDNA6.2/EmGFP-Bsd/V5-DEST vector. Lipofectamine-mediated transfection was performed and stable transfectants were selected. The stable expression of TAGLN in RKO cells was validated by real-time RT PCR, western blotting and immunofluorescence. The Transwell invasion assay, clonogenic survival assay, cell proliferation assay and flow cytometry were performed in the RKO cells with stable expression of TAGLN and the control vector. DNA microarray was used to detect the mRNA expression of the downstream targets of Transgelin in the RKO cells. Results Real-time RT PCR, western blotting and immunofluorescence indicated that the expression of TAGLN increased by 5-fold in the RKO cells transfected with pcDNA6.2/EmGFP-Bsd/V5-TAGLN plasmid as compared to those transfected with the control vector (P63:4650.01). Overexpression of TAGLN increased the invasion by 180% in RKO cells (P63:4650.01), and increased the clonogenic survival by approximately 129% (P63:4650.01). However, overexpression of TAGLN had minimal impact on cell proliferation and apoptosis of RKO cells (P>0.05). Preliminary analysis of the expression microarray of the downstream targets of Transgelin in RKO cells indicated that many cancer-related pathways were involved, notably the integrin-PI3K/Akt pathway, Ras-Rac-JNK pathway and the ezrin-radixin-moesin (ERM) proteins. Conclusion Transgelin was able to promote the invasiveness of human colon cancer cell line RKO in vitro and enhance the clonogenic survival. Transgelin could be a determinant of metastatic potential in human colon cancer cells, which effects through many cancer-related pathways.
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Association of the actin-binding protein Transgelin with lymph node metastasis in human colorectal cancer
Neoplasia, 2009Co-Authors: Ying Lin, Jeffrey R. Lee, Phillip Buckhaults, Hairong Xiong, Christopher Farrell, Robert H. Podolsky, Robert R. Schade, William S. DynanAbstract:Metastatic dissemination of primary tumors is responsible for 90% of colorectal cancer (CRC) deaths. The presence of positive lymph nodes, which separates stage I/II from stage III CRC, is a particularly key factor in patient management. Here, we describe results of a quantitative proteomic survey to identify molecular correlates of node status. Laser capture microdissection and two-dimensional difference gel electrophoresis were used to establish expression profiles for 980 discrete protein features in 24 human CRC specimens. Protein abundances were determined with a median technical coefficient of variation of 10%, which provided an ability to detect small differences between cancer subtypes. Transgelin, a 23-kDa actin-binding protein, emerged as a top-ranked candidate biomarker of node status. The area under the receiver operating characteristic curve for Transgelin in predicting node status was 0.868 (P = .002). Significantly increased frequency of moderate- and high-level Transgelin expression in node-positive CRC was also seen using semiquantitative immunohistochemistry to analyze 94 independent CRC specimens on tissue microarrays (P = .036). Follow-up studies in CRC cell lines demonstrated roles for Transgelin in promoting invasion, survival, and resistance to anoikis. Transgelin localizes to the nucleus of CRC cells, and its sequence and properties suggest that it may participate in regulation of the transcriptional program associated with the epithelial-to-mesenchymal transition.
Qi Kui Chen - One of the best experts on this subject based on the ideXlab platform.
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akt and jnk signaling pathways increase the metastatic potential of colorectal cancer cells by altering Transgelin expression
Digestive Diseases and Sciences, 2016Co-Authors: Huimin Zhou, Yiming Zhang, Qi Kui Chen, Ying LinAbstract:Transgelin (SM22) plays a crucial role in colorectal cancer (CRC) progression; nevertheless, its upstream regulatory mechanisms are poorly defined. AKT and JNK signaling pathways are strongly associated with tumor progression and metastasis, and there are some indications that these pathways might be involved in Transgelin regulation. To examine the role of AKT and JNK signaling in Transgelin regulation in colorectal cancer progression. Phospho-AKT (P-AKT), phospho-JNK (P-JNK), and Transgelin expression were examined in one normal colon cell line (FHC) and three CRC cell lines (SW620, LoVo, and RKO) as well as in normal colon and CRC tissue samples by Western blot and qRT-PCR. Next, siRNA silencing of AKT or JNK pathways in SW620 cells was performed to examine their role in Transgelin regulation. The effects of siRNA silencing on SW620 cell mobility and metastatic properties were examined by cell migration, invasion assays, and actin cytoskeleton. Transgelin, P-AKT, and P-JNK were increased in all examined cell lines. Moreover, Transgelin mRNA and protein expression was especially elevated in SW620 cells. Furthermore, inhibition of Akt or JNK signaling resulted in Transgelin downregulation. When Transgelin, Akt, or JNK signaling was inhibited, SW620 cell migration and invasion were dramatically decreased with inhibition of actin cytoskeleton dynamics. This study demonstrates, for the first time, that activated AKT and JNK signaling pathways promote the overexpression of Transgelin, which potentially contributes to CRC progression and metastasis.
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Transgelin increases metastatic potential of colorectal cancer cells in vivo and alters expression of genes involved in cell motility.
BMC Cancer, 2016Co-Authors: Huimin Zhou, Yuan-yuan Fang, Paul M. Weinberger, Ling Ling Ding, John K. Cowell, Farlyn Z. Hudson, Mingqiang Ren, Jeffrey R. Lee, Qi Kui ChenAbstract:Transgelin is an actin-binding protein that promotes motility in normal cells. Although the role of Transgelin in cancer is controversial, a number of studies have shown that elevated levels correlate with aggressive tumor behavior, advanced stage, and poor prognosis. Here we sought to determine the role of Transgelin more directly by determining whether experimental manipulation of Transgelin levels in colorectal cancer (CRC) cells led to changes in metastatic potential in vivo.
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Additional file 1: Table S1. of Transgelin increases metastatic potential of colorectal cancer cells in vivo and alters expression of genes involved in cell motility
2016Co-Authors: Huimin Zhou, Yuan-yuan Fang, Ling Ling Ding, Mingqiang Ren, Paul Weinberger, John Cowell, Farlyn Hudson, Jeffrey Lee, Qi Kui ChenAbstract:- Comparison of the genes altered by Transgelin overexpression in RKO and DLD-1 cells. Table shows gene symbols, gene names, expression fold changes obtained by cDNA microarray and qPCR in RKO and DLD-1 cells. (DOCX 16Â kb
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P-0193 Transgelin Promotes The Invasiveness of Human Colon Cancer Cells in Vitro
Annals of Oncology, 2012Co-Authors: Ying Lin, Yuan-yuan Fang, Zhou Hui-min, Qi Kui ChenAbstract:ABSTRACT Introduction Transgelin was the top-ranked marker of metastatic potential identified in the comparison of node-positive colorectal cancer (CRC) versus node-negative CRC in our previous study1. Transgelin is localized in the nucleus of cultured CRC cells and microRNA-mediated knockdown of TAGLN (the gene encoding Transgelin) expression modulates the expression of genes involved in the epithelial-to-mesenchymal transition1. This study was initiated to investigate the hallmarks of metastasis in human colon cancer cell line RKO with stable expression of TAGLN in vitro. We also aimed to identify the downstream targets of Transgelin in RKO cells. Methods The plasmid containing human TAGLN was generated using pcDNA6.2/EmGFP-Bsd/V5-DEST vector. Lipofectamine-mediated transfection was performed and stable transfectants were selected. The stable expression of TAGLN in RKO cells was validated by real-time RT PCR, western blotting and immunofluorescence. The Transwell invasion assay, clonogenic survival assay, cell proliferation assay and flow cytometry were performed in the RKO cells with stable expression of TAGLN and the control vector. DNA microarray was used to detect the mRNA expression of the downstream targets of Transgelin in the RKO cells. Results Real-time RT PCR, western blotting and immunofluorescence indicated that the expression of TAGLN increased by 5-fold in the RKO cells transfected with pcDNA6.2/EmGFP-Bsd/V5-TAGLN plasmid as compared to those transfected with the control vector (P63:4650.01). Overexpression of TAGLN increased the invasion by 180% in RKO cells (P63:4650.01), and increased the clonogenic survival by approximately 129% (P63:4650.01). However, overexpression of TAGLN had minimal impact on cell proliferation and apoptosis of RKO cells (P>0.05). Preliminary analysis of the expression microarray of the downstream targets of Transgelin in RKO cells indicated that many cancer-related pathways were involved, notably the integrin-PI3K/Akt pathway, Ras-Rac-JNK pathway and the ezrin-radixin-moesin (ERM) proteins. Conclusion Transgelin was able to promote the invasiveness of human colon cancer cell line RKO in vitro and enhance the clonogenic survival. Transgelin could be a determinant of metastatic potential in human colon cancer cells, which effects through many cancer-related pathways.
Huimin Zhou - One of the best experts on this subject based on the ideXlab platform.
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Transgelin interacts with PARP1 in human colon cancer cells.
Cancer Cell International, 2020Co-Authors: Zhen-xian Lew, Huimin Zhou, Yuan-yuan Fang, Wa Zhong, Xin-yi Yang, Dan-yu Chen, Si-min Luo, Li-fei ChenAbstract:Transgelin, an actin-binding protein, is associated with cytoskeleton remodeling. Findings from our previous studies demonstrated that Transgelin was up-regulated in node-positive colorectal cancer (CRC) versus node-negative disease. Over-expression of TAGLN affected the expression of 256 downstream transcripts and increased the metastatic potential of colon cancer cells in vitro and in vivo. This study aims to explore the mechanisms through which Transgelin participates in the metastasis of colon cancer cells. Immunofluorescence and immunoblotting analysis were used to determine the cellular localization of endogenous and exogenous Transgelin in colon cancer cells. Co-immunoprecipitation and subsequently high-performance liquid chromatography/tandem mass spectrometry were performed to identify the proteins that were potentially interacting with Transgelin. The 256 downstream transcripts regulated by Transgelin were analyzed with bioinformatics methods to discriminate the specific key genes and signaling pathways. The Gene-Cloud of Biotechnology Information (GCBI) tools were used to predict the potential transcription factors (TFs) for the key genes. The predicted TFs corresponded to the proteins identified to interact with Transgelin. The interaction between Transgelin and the TFs was verified by co-immunoprecipitation and immunofluorescence. Transgelin was found to localize in both the cytoplasm and nucleus of the colon cancer cells. Approximately 297 proteins were identified to interact with Transgelin. The overexpression of TAGLN led to the differential expression of 184 downstream genes. Network topology analysis discriminated seven key genes, including CALM1, MYO1F, NCKIPSD, PLK4, RAC1, WAS and WIPF1, which are mostly involved in the Rho signaling pathway. Poly (ADP-ribose) polymerase-1 (PARP1) was predicted as the unique TF for the key genes and concurrently corresponded to the DNA-binding proteins potentially interacting with Transgelin. The interaction between PARP1 and Transgelin in human RKO colon cancer cells was further validated by immunoprecipitation and immunofluorescence assays. Our results suggest that Transgelin binds to PARP1 and regulates the expression of downstream key genes, which are mainly involved in the Rho signaling pathway, and thus participates in the metastasis of colon cancer.
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elevated Transgelin tns1 expression is a potential biomarker in human colorectal cancer
Oncotarget, 2018Co-Authors: Huimin Zhou, Yiming Zhang, Wenrui Xie, Yu Yuan, Yu Chen, Ying LinAbstract:Transgelin is an actin-binding protein that regulates cell motility and other important cellular functions. Previous studies have suggested that Transgelin expression is associated with cancer development and progression, but its specific role in colorectal cancer (CRC) remains controversial. We analyzed expression of Transgelin and its candidate downstream target, tensin 1 (TNS1), in CRC patients using the ONCOMINE, Protein Atlas, and OncoLnc databases. Transgelin and TNS1 mRNA and protein levels were higher in CRC patients and CRC cell lines than in normal tissues and cells. Survival analyses using the OncoLnc database revealed that elevated TAGLN/TNS1 levels were associated with a poor overall survival in CRC patients. Transgelin suppression using siRNA decreased TNS1 expression in CRC cells, demonstrating that Transgelin induces the TNS1 expression. Importantly, suppression of Transgelin or TNS1 using siRNA decreased proliferation and invasiveness of CRC cells. These results suggest that Transgelin/TNS1 signaling promotes CRC cell proliferation and invasion, and that Transgelin/TNS1 expression levels could potentially serve as a prognostic and therapeutic target in CRC patients.
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akt and jnk signaling pathways increase the metastatic potential of colorectal cancer cells by altering Transgelin expression
Digestive Diseases and Sciences, 2016Co-Authors: Huimin Zhou, Yiming Zhang, Qi Kui Chen, Ying LinAbstract:Transgelin (SM22) plays a crucial role in colorectal cancer (CRC) progression; nevertheless, its upstream regulatory mechanisms are poorly defined. AKT and JNK signaling pathways are strongly associated with tumor progression and metastasis, and there are some indications that these pathways might be involved in Transgelin regulation. To examine the role of AKT and JNK signaling in Transgelin regulation in colorectal cancer progression. Phospho-AKT (P-AKT), phospho-JNK (P-JNK), and Transgelin expression were examined in one normal colon cell line (FHC) and three CRC cell lines (SW620, LoVo, and RKO) as well as in normal colon and CRC tissue samples by Western blot and qRT-PCR. Next, siRNA silencing of AKT or JNK pathways in SW620 cells was performed to examine their role in Transgelin regulation. The effects of siRNA silencing on SW620 cell mobility and metastatic properties were examined by cell migration, invasion assays, and actin cytoskeleton. Transgelin, P-AKT, and P-JNK were increased in all examined cell lines. Moreover, Transgelin mRNA and protein expression was especially elevated in SW620 cells. Furthermore, inhibition of Akt or JNK signaling resulted in Transgelin downregulation. When Transgelin, Akt, or JNK signaling was inhibited, SW620 cell migration and invasion were dramatically decreased with inhibition of actin cytoskeleton dynamics. This study demonstrates, for the first time, that activated AKT and JNK signaling pathways promote the overexpression of Transgelin, which potentially contributes to CRC progression and metastasis.
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Transgelin increases metastatic potential of colorectal cancer cells in vivo and alters expression of genes involved in cell motility.
BMC Cancer, 2016Co-Authors: Huimin Zhou, Yuan-yuan Fang, Paul M. Weinberger, Ling Ling Ding, John K. Cowell, Farlyn Z. Hudson, Mingqiang Ren, Jeffrey R. Lee, Qi Kui ChenAbstract:Transgelin is an actin-binding protein that promotes motility in normal cells. Although the role of Transgelin in cancer is controversial, a number of studies have shown that elevated levels correlate with aggressive tumor behavior, advanced stage, and poor prognosis. Here we sought to determine the role of Transgelin more directly by determining whether experimental manipulation of Transgelin levels in colorectal cancer (CRC) cells led to changes in metastatic potential in vivo.
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Additional file 1: Table S1. of Transgelin increases metastatic potential of colorectal cancer cells in vivo and alters expression of genes involved in cell motility
2016Co-Authors: Huimin Zhou, Yuan-yuan Fang, Ling Ling Ding, Mingqiang Ren, Paul Weinberger, John Cowell, Farlyn Hudson, Jeffrey Lee, Qi Kui ChenAbstract:- Comparison of the genes altered by Transgelin overexpression in RKO and DLD-1 cells. Table shows gene symbols, gene names, expression fold changes obtained by cDNA microarray and qPCR in RKO and DLD-1 cells. (DOCX 16Â kb
Pavel Bouchal - One of the best experts on this subject based on the ideXlab platform.
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Transgelin contributes to a poor response of metastatic renal cell carcinoma to sunitinib treatment
Biomedicines, 2021Co-Authors: Pavla Bouchalova, Petr Lapcik, Jindrich Beranek, David Potesil, Jan Podhorec, Alexandr Poprach, Pavel BouchalAbstract:Renal cell carcinoma (RCC) represents about 2–3% of all cancers with over 400,000 new cases per year. Sunitinib, a vascular endothelial growth factor tyrosine kinase receptor inhibitor, has been used mainly for first-line treatment of metastatic clear-cell RCC with good or intermediate prognosis. However, about one-third of metastatic RCC patients do not respond to sunitinib, leading to disease progression. Here, we aim to find and characterize proteins associated with poor sunitinib response in a pilot proteomics study. Sixteen RCC tumors from patients responding (8) vs. non-responding (8) to sunitinib 3 months after treatment initiation were analyzed using data-independent acquisition mass spectrometry, together with their adjacent non-cancerous tissues. Proteomics analysis quantified 1996 protein groups (FDR = 0.01) and revealed 27 proteins deregulated between tumors non-responding vs. responding to sunitinib, representing a pattern of deregulated proteins potentially contributing to sunitinib resistance. Gene set enrichment analysis showed an up-regulation of epithelial-to-mesenchymal transition with Transgelin as one of the most significantly abundant proteins. Transgelin expression was silenced by CRISPR/Cas9 and RNA interference, and the cells with reduced Transgelin level exhibited significantly slower proliferation. Our data indicate that Transgelin is an essential protein supporting RCC cell proliferation, which could contribute to intrinsic sunitinib resistance.
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dia ms identifies and validates Transgelin as protein contributing to a poor response of metastatic renal cell carcinoma to sunitinib treatment
2021Co-Authors: Pavla Bouchalova, Petr Lapcik, Jindrich Beranek, Jan Podhorec, Alexandr Poprach, David Potěsil, Milan Hora, Ondřej Fiala, Pavel BouchalAbstract:Introduction. Renal cell carcinoma (RCC) represents about 2–3% of all cancers with over 400,000 new cases per year. Sunitinib, a vascular endothelial growth factor tyrosine kinase receptor inhibitor, has been used mainly for first-line treatment of metastatic clear-cell RCC (mccRCC) with good or intermediate prognosis. However, about one-third of mccRCC patients do not respond to sunitinib, leading to disease progression. Methods. Here, we aim to find and characterize proteins associated with poor sunitinib response. Sixteen RCC tumors from patients responding (8) vs. non-responding (8) to sunitinib 3 months after treatment initiation were analyzed using data-independent acquisition mass spectrometry (DIA-MS) on Impact II LC-MS system (Bruker), together with their adjacent non-cancerous tissues in a pilot proteomics study. Validation was performed in an independent cohort of 75 mccRCC patients using DIA-MS on QExactive HF-X (Thermo Fisher Scientific), with data analysis in Spectronaut 13.9 (Biognosys). Transgelin protein role was functionally analyzed in RCC cell lines using CRISPR and RNAi silencing techniques. Results. Proteomics analysis quantified 1996 protein groups (FDR=0.01) and revealed 27 proteins deregulated between tumors non-responding vs. responding to sunitinib in the pilot study, representing a pattern of proteins potentially contributing to sunitinib resistance. Validation cohort confirmed up-regulation of Transgelin in tumors non-responding to sunitinib and revealed its association with tumor grade. Gene set enrichment analysis showed an up-regulation of epithelial-to-mesenchymal transition with Transgelin as one of the most significantly abundant proteins. Reduced Transgelin protein level in CRISPR and RNAi altered RCC cells led to significantly slower proliferation of these cells and affected their survival. Conclusion. Altogether, our data indicate that Transgelin is an essential protein supporting RCC cell proliferation, which could contribute to intrinsic sunitinib resistance, and is associated with aggressive phenotype of RCC tumors.
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Transgelin Silencing Induces Different Processes in Different Breast Cancer Cell Lines
PROTEOMICS, 2020Co-Authors: Monika Dvorakova, Petr Lapcik, Pavla Bouchalova, Pavel BouchalAbstract:Transgelin is a protein reported to be a marker of several cancers. However, previous studies have shown both up- and down-regulation of Transgelin in tumors when compared with non-tumor tissues and the mechanisms whereby Transgelin may affect the development of cancer remain largely unknown. Transgelin is especially abundant in smooth muscle cells and is associated with actin stress fibers. These contractile structures participate in cell motility, adhesion, and the maintenance of cell morphology. Here, the role of Transgelin in breast cancer is focused on. Initially, the effects of Transgelin on cell migration of the breast cancer cell lines, BT 549 and PMC 42, is studied. Interestingly, Transgelin silencing increased the migration of PMC 42 cells, but decreased the migration of BT 549 cells. To clarify these contradictory results, the changes in protein abundances after Transgelin silencing in these two cell lines are analyzed using quantitative proteomics. The results confirmed the role of Transgelin in the migration of BT 549 cells and suggest the involvement of Transgelin in apoptosis and small molecule biochemistry in PMC 42 cells. The context-dependent function of Transgelin reflects the different molecular backgrounds of these cell lines, which differ in karyotypes, mutation statuses, and proteome profiles.
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Transgelin is upregulated in stromal cells of lymph node positive breast cancer
Journal of Proteomics, 2016Co-Authors: Monika Dvořáková, Juraj Lenčo, Rudolf Nenutil, Jarmila Jeřábková, Iva Procházková, Pavel BouchalAbstract:Abstract Transgelin and Transgelin-2 have been discussed as potential markers of various cancers. Here we identified increased Transgelin level in lymph node positive vs. negative, low grade primary breast cancer tissues using 2-DE in the cohort of 12 patients. We further clinically validated 2-DE results in an independent cohort of 48 low grade breast cancer patients through untargeted and targeted proteomics analysis (iTRAQ-2D-LC–MS/MS, mTRAQ-SRM), at transcript level and using immunohistochemistry. Another group of 48 high grade tumors of different breast cancer subtypes was analyzed together with the low grade samples to test Transgelin specificity for low grade tumors and to study Transgelin relation to known molecular markers and histological features. The results confirmed Transgelin connection with the lymph node metastasis. As a marker of a reactive tumor stroma, Transgelin can be connected with the higher risk of metastasis development. Moreover, we observed significant down-regulation of Transgelin in high vs. low grade tumors caused by decreased content of stromal cells (mainly expressing Transgelin) in high grade tumor tissue. We also analyzed expression of Transgelin-2 in the second cohort using proteomics and immunohistochemistry. Transgelin-2 was mainly expressed by epithelial cancer cells and its levels were increased in metastatic and poorly differentiated tumors. Biological significance Both Transgelin and Transgelin-2 have been previously described as potential markers of many types of cancer. We are specifying this connection to metastatic affection of lymph nodes and cell differentiation in breast cancer. In the wider context, the results of our study highlight tumor stroma as a source of cancer biomarkers and point out how measured levels of tissue markers can actually reflect cellular feature of cancer mass.
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Transgelins cytoskeletal proteins implicated in different aspects of cancer development
Expert Review of Proteomics, 2014Co-Authors: Monika Dvorakova, Rudolf Nenutil, Pavel BouchalAbstract:Transgelin is an abundant protein of smooth muscle cells, where its role has been primarily studied. As a protein affecting dynamics of the actin cytoskeleton via stabilization of actin filaments, Transgelin is both directly and indirectly involved in many cancer-related processes such as migration, proliferation, differentiation or apoptosis. Transgelin was previously reviewed as a tumor suppressor; however, recent data based on a number of proteomics studies indicate its pro-tumorigenic role, for example, in colorectal or hepatocellular cancer. We summarize these contradictory observations in both clinical and functional proteomics projects and analyze the role of Transgelin in tumors in detail. Generally, the expression and biological role of Transgelin seem to differ among various types of tumor cells and stroma, and possibly change during tumor progression. We also overview the recent data on Transgelin-2, a sequence homolog of Transgelin, whose role in the tumor development might be contradictory to the role of Transgelin.
