The Experts below are selected from a list of 189 Experts worldwide ranked by ideXlab platform
Cecilia Williams - One of the best experts on this subject based on the ideXlab platform.
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mir 206 inhibits cell migration through direct targeting of the actin binding protein coronin 1c in triple negative breast cancer
Molecular Oncology, 2014Co-Authors: Jun Wang, Efrosini Tsouko, Philip Jonsson, Jonas Bergh, Johan Hartman, Eylem Aydogdu, Cecilia WilliamsAbstract:Patients with triple-negative breast cancer (TNBC) have an overall poor prognosis, which is primarily due to a high metastatic capacity of these tumors. Novel therapeutic approaches to target the signaling pathways that promote Metastasis are desirable, in order to improve the outcome for these patients. A loss of function of a microRNA, miR-206, is related to increased Metastasis Potential in breast cancers but the mechanism is not known. In this study, we show that miR-206 was decreased in TNBC clinical tumor samples and cell lines whereas one of its predicted targets, actin-binding protein CORO1C, was increased. Expression of miR-206 significantly reduced proliferation and migration while repressing CORO1C mRNA and protein levels. We demonstrate that miR-206 interacts with the 3'-untranslated region (3'-UTR) of CORO1C and regulates this gene post-transcriptionally. This post-transcriptional regulation was dependent on two miR-206-binding sites within the 3'-UTR of CORO1C and was relieved by mutations of corresponding sites. Further, silencing of CORO1C reduced tumor cell migration and affected the actin skeleton and cell morphology, similar to miR-206 expression, but did not reduce proliferation. In accordance with this, overexpression of CORO1C rescued the inhibitory effect of miR-206 on cell migration. Our findings suggest that miR-206 represses tumor cell migration through direct targeting of CORO1C in TNBC cells which modulates the actin filaments. This pathway is a novel mechanism that offers a mechanistic basis through which the metastatic Potential of TNBC tumors could be targeted.
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abstract p4 07 12 mir 206 inhibits cell migration through direct targeting of the actin binding protein coronin 1c in triple negative breast cancer
Cancer Research, 2013Co-Authors: Jun Wang, Efrosini Tsouko, Philip Jonsson, Jonas Bergh, Johan Hartman, Eylem Aydogdu, Cecilia WilliamsAbstract:Patients with triple-negative breast cancer (TNBC) have an overall poor prognosis, which is primarily due to a high metastatic capacity of these tumors. Novel therapeutic approaches to target the signaling pathways that promote Metastasis are desirable, in order to improve the outcome of TNBC patients. A loss of function of a microRNA, miR-206, is related to increased Metastasis Potential in breast cancers but the mechanism remains to be elucidated. In this study, we show that miR-206 was decreased in TNBC clinical tumor samples and cell lines whereas one of its predicted targets, actin-binding protein CORO1C, was increased. Expression of miR-206 significantly reduced proliferation by inducing a G1-S cell cycle arrest and migration and also repressed CORO1C mRNA and protein levels. We demonstrate that miR-206 interacts with the 3’-untranslated region (3’-UTR) of CORO1C and regulates this gene post-transcriptionally. Further, silencing of CORO1C reduced tumor cell migration and affected the actin skeleton and cell morphology, similar to miR-206 expression, but did not reduce proliferation. Our findings suggest that miR-206 targets CORO1C in TNBC cells, thereby affecting the actin filaments which results in a repressed tumor cell migration. This pathway is a novel mechanism offering a mechanistic basis whereby the metastatic Potential of TNBC tumors could be targeted. Citation Information: Cancer Res 2013;73(24 Suppl): Abstract nr P4-07-12.
Qinghua Zhou - One of the best experts on this subject based on the ideXlab platform.
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mir 26a enhances Metastasis Potential of lung cancer cells via akt pathway by targeting pten
Biochimica et Biophysica Acta, 2012Co-Authors: Boning Liu, Bin Liu, Changli Wang, Yunde Liu, Qinghua ZhouAbstract:Lung cancer is the leading cause of cancer related death, 90% of lung cancer patients die of Metastasis. Many microRNAs (miRNAs) are deregulated in cancer. They are involved in tumorigenesis and function as oncogenes or tumor suppressor genes. Recent studies show that miRNAs may be responsible for tumor Metastasis. Several functional studies show that miR-26a plays an important role in carcinogenesis; however, none of these studies is related to tumor Metastasis. In the present study, we investigated the effect of miR-26a on Metastasis Potential of lung cancer cells. Our data showed that miR-26a expression level was higher in lymph node Metastasis tumor tissues than in primary tumor tissues. Ectopic expression of miR-26a dramatically enhanced lung cancer cell migration and invasion abilities. Metastasis-related genes matrix metallopeptidase 2 (MMP-2), vascular endothelial growth factor (VEGF), Twist and β-catenin were upregulated. Phosphatase and tensin homolog (PTEN) was a direct target of miR-26a. Further mechanistic study revealed that miR-26a increased AKT phosphorylation and nuclear factor kappa B (NFκB) transcriptional activation. Our study demonstrated that miR-26a enhanced lung cancer cell Metastasis Potential via modulation of Metastasis-related gene expression, and activation of AKT pathway by PTEN suppression, suggesting that miR-26a might be a Potential therapeutic candidate in patients with metastatic lung cancer.
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isothiocyanates induce oxidative stress and suppress the Metastasis Potential of human non small cell lung cancer cells
BMC Cancer, 2010Co-Authors: Yu Zhu, Boning Liu, Huiqin Yan, Qinghua ZhouAbstract:Isothiocyanates are natural compounds found in consumable cruciferous vegetables. They have been shown to inhibit chemical carcinogenesis by a wide variety of chemical carcinogens in animal models. Recent studies have also shown that isothiocyanates have antitumor activity, inhibiting the growth of several types of cultured human cancer cells. Our previous study showed that PEITC inhibited human leukemia cells growth by inducing apoptosis. However, the effect of isothiocyanates on lung cancer cell Metastasis has not been studied. In the present study, we investigated the inhibitory effects of BITC and PEITC on metastatic Potential of highly metastatic human lung cancer L9981 cells. Cell migration and invasion were measured by wound healing assay and transwell chemotaxis assay. Expression of Metastasis-related genes was assessed by quantitative RT-PCR and Western blotting. The mechanisms of action were evaluated by flow cytometry, reporter assay and Western blotting. Our data showed that both BITC and PEITC inhibited L9981 cell growth in a dose-dependent manner, the IC50 values were 5.0 and 9.7 μM, respectively. Cell migrations were reduced to 8.1% and 16.5% of control, respectively; and cell invasions were reduced to 2.7% and 7.3% of control, respectively. Metastasis-related genes MMP-2, Twist and β-catenin were also modulated. BITC and PEITC inhibited cell survival signaling molecules Akt and NFκB activation. Moreover, BITC and PEITC increased ROS generation and caused GSH depletion. Pretreatment with NAC blocked BITC and PEITC induced ROS elevation and NFκB inhibition. Our results indicated that BITC and PEITC suppress lung cancer cell Metastasis Potential by modulation of Metastasis-related gene expression, inhibition of Akt/NFκB pathway. Induction of oxidative stress may play an important role.
Jun Wang - One of the best experts on this subject based on the ideXlab platform.
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mir 206 inhibits cell migration through direct targeting of the actin binding protein coronin 1c in triple negative breast cancer
Molecular Oncology, 2014Co-Authors: Jun Wang, Efrosini Tsouko, Philip Jonsson, Jonas Bergh, Johan Hartman, Eylem Aydogdu, Cecilia WilliamsAbstract:Patients with triple-negative breast cancer (TNBC) have an overall poor prognosis, which is primarily due to a high metastatic capacity of these tumors. Novel therapeutic approaches to target the signaling pathways that promote Metastasis are desirable, in order to improve the outcome for these patients. A loss of function of a microRNA, miR-206, is related to increased Metastasis Potential in breast cancers but the mechanism is not known. In this study, we show that miR-206 was decreased in TNBC clinical tumor samples and cell lines whereas one of its predicted targets, actin-binding protein CORO1C, was increased. Expression of miR-206 significantly reduced proliferation and migration while repressing CORO1C mRNA and protein levels. We demonstrate that miR-206 interacts with the 3'-untranslated region (3'-UTR) of CORO1C and regulates this gene post-transcriptionally. This post-transcriptional regulation was dependent on two miR-206-binding sites within the 3'-UTR of CORO1C and was relieved by mutations of corresponding sites. Further, silencing of CORO1C reduced tumor cell migration and affected the actin skeleton and cell morphology, similar to miR-206 expression, but did not reduce proliferation. In accordance with this, overexpression of CORO1C rescued the inhibitory effect of miR-206 on cell migration. Our findings suggest that miR-206 represses tumor cell migration through direct targeting of CORO1C in TNBC cells which modulates the actin filaments. This pathway is a novel mechanism that offers a mechanistic basis through which the metastatic Potential of TNBC tumors could be targeted.
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abstract p4 07 12 mir 206 inhibits cell migration through direct targeting of the actin binding protein coronin 1c in triple negative breast cancer
Cancer Research, 2013Co-Authors: Jun Wang, Efrosini Tsouko, Philip Jonsson, Jonas Bergh, Johan Hartman, Eylem Aydogdu, Cecilia WilliamsAbstract:Patients with triple-negative breast cancer (TNBC) have an overall poor prognosis, which is primarily due to a high metastatic capacity of these tumors. Novel therapeutic approaches to target the signaling pathways that promote Metastasis are desirable, in order to improve the outcome of TNBC patients. A loss of function of a microRNA, miR-206, is related to increased Metastasis Potential in breast cancers but the mechanism remains to be elucidated. In this study, we show that miR-206 was decreased in TNBC clinical tumor samples and cell lines whereas one of its predicted targets, actin-binding protein CORO1C, was increased. Expression of miR-206 significantly reduced proliferation by inducing a G1-S cell cycle arrest and migration and also repressed CORO1C mRNA and protein levels. We demonstrate that miR-206 interacts with the 3’-untranslated region (3’-UTR) of CORO1C and regulates this gene post-transcriptionally. Further, silencing of CORO1C reduced tumor cell migration and affected the actin skeleton and cell morphology, similar to miR-206 expression, but did not reduce proliferation. Our findings suggest that miR-206 targets CORO1C in TNBC cells, thereby affecting the actin filaments which results in a repressed tumor cell migration. This pathway is a novel mechanism offering a mechanistic basis whereby the metastatic Potential of TNBC tumors could be targeted. Citation Information: Cancer Res 2013;73(24 Suppl): Abstract nr P4-07-12.
Zhaoyou Tang - One of the best experts on this subject based on the ideXlab platform.
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radiation enhances long term Metastasis Potential of residual hepatocellular carcinoma in nude mice through tmprss4 induced epithelial mesenchymal transition
Cancer Gene Therapy, 2011Co-Authors: Z C Zeng, Lu Wang, Shuangjian Qiu, J W Zhou, Xuting Zhi, Zhaoyou TangAbstract:Recurrence and Metastasis are frequently observed after radiotherapy for hepatocellular carcinoma (HCC), although upregulation of matrix metalloproteinases (MMPs) and vascular endothelial growth factor (VEGF) induced by radiation has been claimed to be involved, the mechanism is not clarified yet. In the present study, by using MHCC97L, a human HCC cell line with metastatic Potential, and its xenograft in nude mice, we found that radiation induced a 48- to 72-h temporary increase in the expression of MMP-2 and VEGF both in vitro and in vivo, but only the in vitro invasiveness of MHCC97L cells was enhanced, while the in vivo metastatic Potential of tumors was suppressed. Whereas, 30 days after radiation, when the expression of MMP-2 and VEGF decreased to unirradiated control levels, the in vivo dissemination and metastatic Potential of residual tumors have just begun to increase with overexpression of TMPRSS4, which induced loss of E-cadherin through induction of Smad-Interacting Protein 1 (SIP1), an E-cadherin transcriptional repressor, and led to epithelial-mesenchymal transition (EMT). This process was blocked by treatment of siRNA-TMPRSS4. In conclusion, our study revealed novel findings regarding the biphasic effect of radiation on the metastatic Potential of residual HCC. Overexpression of TMPRSS4 has a critical role in radiation-induced long-term dissemination and Metastasis of residual HCC by facilitating EMT. These findings may provide new clues to suppress the radiation-induced dissemination and Metastasis, thereby improve the prognosis of HCC patients.
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serum cyfra 21 1 level reflects hepatocellular carcinoma Metastasis study in nude mice model and clinical patients
Journal of Cancer Research and Clinical Oncology, 2006Co-Authors: Zhaoyou Tang, Bo Tian, Lunxiu Qin, Qiong Xue, Ruixia SunAbstract:Our previous proteomics study on human hepatocellular carcinoma (HCC) cell strains revealed that cytokeratin 19 (CK19) was expressed in cells with high Metastasis Potential; we further studied serum CK19 fragment CYFRA 21-1 level in HCC patients and nude mice model of HCC Metastasis. HCC cell line HCCLM3 was injected subcutaneously into 30 nude mice which were then randomized into 6 groups of 5 mice each. The murine serum CYFRA 21-1 and pulmonary metastases were determined 2, 3, 4, 5, 6, and 7 weeks after injection. Serum CYFRA 21-1 levels of 101 normal controls and 108 HCC patients were also determined. In nude mice model, CYFRA 21-1 level increased significantly when pulmonary metastases occurred. Among 108 HCC patients, 24 (22.2%) had increased serum CYFRA 21-1 level. The presence of portal vein tumor emboli was significantly higher in CYFRA 21-1 increased cases (33.3%, 6/24) than in CYFRA 21-1 normal cases (6.0%, 5/84) (x2 = 7.403, P < 0.01). In addition, the percentage of TNM stage III/IV tumor was significantly higher in CYFRA 21-1 increased patients (54.2%, 13/24) than in CYFRA 21-1 normal cases (21.4%, 18/84) (x2 = 9.776, P < 0.005). These results suggest that CK19 may play an important role in HCC Metastasis.
Jian Zhou - One of the best experts on this subject based on the ideXlab platform.
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slc34a2 simultaneously promotes papillary thyroid carcinoma growth and invasion through distinct mechanisms
Oncogene, 2020Co-Authors: Jing He, Tengfei Xing, Mingxia Zhou, Siwen Gu, Xiaoyan Li, Fei Gu, Wei Chen, Jian ZhouAbstract:Thyroid cancer is the fastest growing cancer among all solid tumors in recent decades. Papillary thyroid carcinoma (PTC) is the most predominant type of thyroid cancer. Around 30% of PTC patients with distant metastases and local invasion receive poor prognosis. Thus, the identification of new druggable biological targets is of great importance. Accumulating evidence indicates that solute carrier family numbers have emerged as obligate effectors during the progression of multiple malignancies. Here, we uncovered the functional significance, molecular mechanisms, and clinical impact of solute carrier family 34 member A2 (SLC34A2) in PTC. SLC34A2 was markedly overexpressed in PTC tissues at both mRNA and protein levels compared with matched adjacent normal tissues due to promoter hypomethylation mediated by the DNA methyltransferase 3 beta (DNMT3B). Furthermore, a series of in vivo and in vitro gain- or loss-of-functional assays elucidated the role of SLC34A2 in boosting cell proliferation, cell cycle progression, migration, invasion, and adhesion of PTC cells. Using immunoprecipitation and mass spectrometry, we discovered that SLC34A2 bound to the actin-binding repeats domain of Cortactin (CTTN), thereby inducing the invadopodia formation of PTC cells to promote the Metastasis Potential of PTC cells. Besides, our mechanistic studies, as well as gene set enrichment analysis (GSEA), have pinpointed the PTEN/AKT/FOXO3a pathway as a major signaling functioning downstream of SLC34A2 regulated cell growth. Taken together, our results highlighted that SLC34A2 plays a pivotal oncogenic role during carcinogenesis and Metastasis through distinct mechanisms in PTC.
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microrna 30a suppresses autophagy mediated anoikis resistance and Metastasis in hepatocellular carcinoma
Cancer Letters, 2018Co-Authors: Yinghong Shi, Jian Zhou, Yuanfei Peng, Weiren Liu, Guoming Shi, Qiang Gao, Xiaoying Wang, Kang Song, Jia Fan, Zhenbin DingAbstract:Abstract MiRNA-30a (miR-30a) was previously reported as one of metastatic hepatocellular carcinoma (HCC)-related microRNAs. However, the function of miR-30a on enhancing our biological understanding of HCC Metastasis is not clear. This study demonstrated that miR-30a was significantly down-regulated in HCC tissues and cell lines, and was associated with vascular invasion, Metastasis Potential and recurrent disease in HCC. Functional studies confirmed that miR-30a could inhibit the Metastasis of HCC in a well-established nude mouse model of lung Metastasis. Moreover, miR-30a was proved to prevent anoikis inhibition of HCC cells in vivo and in vitro. Mechanically, autophagy related protein Beclin 1 and Atg5 were direct downstream targets of miR-30a, and mediated autophagy activity influence of miR-30a in HCC. Taken together, downregulated miR-30a in metastatic HCC mediates Beclin 1 and Atg5-dependent autophagy, which confers anoikis resistance in HCC cells. The molecular basis of autophagy action during this process partly contributes to the HCC Metastasis, suggesting that targeting autophagy via miR-30a may have therapeutic implications for the prevention of HCC recurrence/Metastasis.