The Experts below are selected from a list of 65310 Experts worldwide ranked by ideXlab platform

Wen-tao Zhao - One of the best experts on this subject based on the ideXlab platform.

  • Klf4 reduces stemness phenotype, triggers Mesenchymal-Epithelial Transition (MET)-like molecular changes, and prevents tumor progression in nasopharygeal carcinoma
    Oncotarget, 2017
    Co-Authors: Xiqing Li, Zhunlan Zhao, Xiao-ling Zhang, Sheng Yang, Xinglong Yang, Sheng-chun Wang, Wen-tao Zhao
    Abstract:

    // Xiqing Li 1, 2, 3, * , Zhunlan Zhao 1, 3, * , Xiaoling Zhang 4, * , Sheng Yang 1, * , Xia Lin 1 , Xinglong Yang 1 , Xiaolin Lin 1 , Junwen Shi 1 , Shengchun Wang 1 , Wentao Zhao 1 , Jing Li 1 , Fei Gao 1, 7 , Mingyue Liu 3 , Ning Ma 3 , Weiren Luo 8 , Kaitai Yao 1 , Yan Sun 6 , Shengjun Xiao 5 , Dong Xiao 1, 2 and Junshuang Jia 1 1 Guangdong Provincial Key Laboratory of Cancer Immunotherapy Research and Guangzhou Key Laboratory of Tumor Immunology Research, Cancer Research Institute, Southern Medical University, Guangzhou 510515, China 2 Institute of Comparative Medicine & Laboratory Animal Center, Southern Medical University, Guangzhou 510515, China 3 Department of Oncology, The People’s Hosptial of Zhengzhou University, Zhengzhou 450003, China 4 Department of Physiology, Faculty of Basic Medical Sciences, Guilin Medical University, Guilin 541004, China 5 Department of Pathology, The Second Affiliated Hospital, Guilin Medical University, Guilin 541199, China 6 Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou 510080, China 7 Department of Gastroenterology, The First Affiliated Hospital of Jinan University, Guangzhou 510630, China 8 The Third People's Hospital of Shenzhen, Guangdong Medical University, Shenzhen 518112, China * These authors have contributed equally to this work Correspondence to: Dong Xiao, email: xiao_d@hotmail.com Shengjun Xiao, email: xiaoshengjun@glmc.edu.cn Junshuang Jia, email: Jiajsh4@126.com Keywords: Klf4, nasopharyngeal carcinoma (NPC), stemness, epithelial-mesenchymal Transition (EMT), cancer invasion and metastasis Received: March 31, 2017      Accepted: June 29, 2017      Published: September 27, 2017 ABSTRACT The reprogramming factor Kruppel-like factor 4 (Klf4), one of the Yamanaka's reprogramming factors, plays an essential role in reprogramming somatic cells into induced pluripotent stem cells (iPSCs). Klf4 is dysregulated and displays divergent functions in multiple malignancies, but the biological roles of Klf4 in nasopharyngeal carcinoma (NPC) remain unknown. The present study revealed that Klf4 downregulation in a cohort of human NPC biopsies is significantly associated with invasive and metastatic phenotypes of NPC. Our results showed exogenous expression of Klf4 significantly inhibited cell proliferation, decreased stemness, triggered Mesenchymal-Epithelial Transition (MET)-like molecular changes, and suppressed migration and invasion of NPC cells, whereas depletion of endogeneous Klf4 by RNAi reversed the aforementioned biological behaviors and characheristics. Klf4 silencing significantly enhanced the metastatic ability of NPC cells in vivo . In addition, CHIP assay confirmed that E-cadherin is a transcriptional target of Klf4 in NPC cells. Additional studies demonstrated that Klf4-induced MET-like cellular marker alterations, and reduced motility and invasion of NPC cells were mediated by E-cadherin. This study revealed the clinical correlation between Klf4 expression and epithelial-mesenchymal Transition (EMT) biomarkers (including its target gene E-cadherin) in a cohort of NPC biopsies. Taken together, our findings suggest, for what we believe is the first time, that Klf4 functions as a tumor suppressor in NPC to decrease stemness phenotype, inhibit EMT and prevent tumor progression, suggesting that restoring Klf4 function may provide therapeutic benefits in NPC.

  • microrna 122 triggers mesenchymal epithelial Transition and suppresses hepatocellular carcinoma cell motility and invasion by targeting rhoa
    PLOS ONE, 2014
    Co-Authors: Sheng-chun Wang, Sheng Yang, Wen-tao Zhao, Xiaolin Lin, Tingting Zhang, Huiyan Wang, Junwen Shi, Raoying Xie, Fang Wei, Yujuan Qin
    Abstract:

    The loss of microRNA-122 (miR-122) expression is strongly associated with increased invasion and metastasis, and poor prognosis of hepatocellular carcinoma (HCC), however, the underlying mechanisms remain poorly understood. In the present study, we observed that miR-122 over-expression in HCC cell lines Sk-hep-1 and Bel-7402 triggered the Mesenchymal-Epithelial Transition (MET), as demonstrated by epithelial-like morphological changes, up-regulated epithelial proteins (E-cadherin, ZO-1, α-catenin, occludin, BVES, and MST4), and down-regulated mesenchymal proteins (vimentin and fibronectin). The over-expression of miRNA-122 also caused cytoskeleton disruption, RhoA/Rock pathway inactivation, enhanced cell adhesion, and suppression of migration and invasion of Sk-hep-1 and Bel-7402 cells, whereas, these effects could be reversed through miR-122 inhibition. Additional studies demonstrated that the inhibition of wild-type RhoA function induced MET and inhibited cell migration and invasion, while RhoA over-expression reversed miR-122-induced MET and inhibition of migration and invasion of HCC cells, suggesting that miR-122 induced MET and suppressed the migration and invasion of HCC cells by targeting RhoA. Moreover, our results demonstrated that HNF4α up-regulated its target gene miR-122 that subsequently induced MET and inhibited cell migration and invasion, whereas miR-122 inhibition reversed these HNF4α-induced phenotypes. These results revealed functional and mechanistic links among the tumor suppressors HNF4α, miR-122, and RhoA in EMT and invasive and metastatic phenotypes of HCC. Taken together, our study provides the first evidence that the HNF4α/miR-122/RhoA axis negatively regulates EMT and the migration and invasion of HCC cells.

  • The enforced expression of c-Myc in pig fibroblasts triggers Mesenchymal-Epithelial Transition (MET) via F-actin reorganization and RhoA/Rock pathway inactivation.
    Cell cycle (Georgetown Tex.), 2013
    Co-Authors: Junwen Shi, Sheng-chun Wang, Xiaolin Lin, Tingting Zhang, Wei Liu, Junshuang Jia, Hong-fen Sheng, Zhi-fang Yao, Wen-tao Zhao
    Abstract:

    In previous studies from other labs it has been well demonstrated that the ectopic expression of c-Myc in mammary epithelial cells can induce epithelial-mesenchymal Transition (EMT), whereas in our pilot experiment, epithelial-like morphological changes were unexpectedly observed in c-Myc-expressing pig fibroblasts [i.e., porcine embryonic fibroblasts (PEFs) and porcine dermal fibroblasts (PDFs)] and pig mesenchymal stem cells, suggesting that the same c-Myc gene is entitled to trigger EMT in epithelial cells and Mesenchymal-Epithelial Transition (MET) in fibroblasts. This prompted us to characterize the existence of a MET in c-Myc-expressing PEFs and PDFs at the molecular level. qRT-PCR, immunofluorescence and western blot analysis illustrated that epithelial-like morphological changes were accompanied by the increased expression of epithelial markers [such as cell adhesion proteins (E-cadherin, α-catenin and Bves), tight junction protein occludin and cytokeratins (Krt8 and Krt18)], the reduced expression of mesenchymal markers [vimentin, fibronectin 1 (FN1), snail1, collagen family of proteins (COL1A1, COL5A2) and matrix metalloproteinase (MMP) family (MMP12 and MMP14)] and the decreased cell motility and increased cell adhesion in c-Myc-expressing PEFs and PDFs. Furthermore, the ectopic expression of c-Myc in pig fibroblasts disrupted the stress fiber network, suppressed the formation of filopodia and lamellipodia, and resulted in RhoA/Rock pathway inactivation, which finally participates in epithelial-like morphological conversion. Taken together, these findings demonstrate, for the first time, that the enforced expression of c-Myc in fibroblasts can trigger MET, to which cytoskeleton depolymerization and RhoA/Rock pathway inactivation contribute.

Daohai Zhang - One of the best experts on this subject based on the ideXlab platform.

Nandini Mondal - One of the best experts on this subject based on the ideXlab platform.

  • bone vascular niche e selectin induces mesenchymal epithelial Transition and wnt activation in cancer cells to promote bone metastasis
    Nature Cell Biology, 2019
    Co-Authors: Mark Esposito, Nandini Mondal, Todd M Greco, Chiara Spadazzi, Hanqiu Zheng, Corey Cheung, John Magnani, Ileana M Cristea, Robert Sackstein
    Abstract:

    How disseminated tumour cells engage specific stromal components in distant organs for survival and outgrowth is a critical but poorly understood step of the metastatic cascade. Previous studies have demonstrated the importance of the epithelial–mesenchymal Transition in promoting the cancer stem cell properties needed for metastasis initiation, whereas the reverse process of mesenchymal–epithelial Transition is required for metastatic outgrowth. Here we report that this paradoxical requirement for the simultaneous induction of both mesenchymal–epithelial Transition and cancer stem cell traits in disseminated tumour cells is provided by bone vascular niche E-selectin, whose direct binding to cancer cells promotes bone metastasis by inducing mesenchymal–epithelial Transition and activating Wnt signalling. E-selectin binding activity mediated by the α1-3 fucosyltransferases Fut3/Fut6 and Glg1 are instrumental to the formation of bone metastasis. These findings provide unique insights into the functional role of E-selectin as a component of the vascular niche critical for metastatic colonization in bone. Esposito et al. report a role for bone vascular niche E-selectin in promoting mesenchymal–epithelial Transition and Wnt signalling in breast cancer cells, thereby enhancing bone metastasis.

  • Bone vascular niche E-selectin induces mesenchymal–epithelial Transition and Wnt activation in cancer cells to promote bone metastasis
    Nature cell biology, 2019
    Co-Authors: Mark Esposito, Nandini Mondal, Todd M Greco, Chiara Spadazzi, Hanqiu Zheng, Corey Cheung, Yong Wei, Song Chang Lin, John L. Magnani, Sue Hwa Lin
    Abstract:

    How disseminated tumour cells engage specific stromal components in distant organs for survival and outgrowth is a critical but poorly understood step of the metastatic cascade. Previous studies have demonstrated the importance of the epithelial–mesenchymal Transition in promoting the cancer stem cell properties needed for metastasis initiation, whereas the reverse process of mesenchymal–epithelial Transition is required for metastatic outgrowth. Here we report that this paradoxical requirement for the simultaneous induction of both mesenchymal–epithelial Transition and cancer stem cell traits in disseminated tumour cells is provided by bone vascular niche E-selectin, whose direct binding to cancer cells promotes bone metastasis by inducing mesenchymal–epithelial Transition and activating Wnt signalling. E-selectin binding activity mediated by the α1-3 fucosyltransferases Fut3/Fut6 and Glg1 are instrumental to the formation of bone metastasis. These findings provide unique insights into the functional role of E-selectin as a component of the vascular niche critical for metastatic colonization in bone. Esposito et al. report a role for bone vascular niche E-selectin in promoting mesenchymal–epithelial Transition and Wnt signalling in breast cancer cells, thereby enhancing bone metastasis.

Mark Esposito - One of the best experts on this subject based on the ideXlab platform.

  • bone vascular niche e selectin induces mesenchymal epithelial Transition and wnt activation in cancer cells to promote bone metastasis
    Nature Cell Biology, 2019
    Co-Authors: Mark Esposito, Nandini Mondal, Todd M Greco, Chiara Spadazzi, Hanqiu Zheng, Corey Cheung, John Magnani, Ileana M Cristea, Robert Sackstein
    Abstract:

    How disseminated tumour cells engage specific stromal components in distant organs for survival and outgrowth is a critical but poorly understood step of the metastatic cascade. Previous studies have demonstrated the importance of the epithelial–mesenchymal Transition in promoting the cancer stem cell properties needed for metastasis initiation, whereas the reverse process of mesenchymal–epithelial Transition is required for metastatic outgrowth. Here we report that this paradoxical requirement for the simultaneous induction of both mesenchymal–epithelial Transition and cancer stem cell traits in disseminated tumour cells is provided by bone vascular niche E-selectin, whose direct binding to cancer cells promotes bone metastasis by inducing mesenchymal–epithelial Transition and activating Wnt signalling. E-selectin binding activity mediated by the α1-3 fucosyltransferases Fut3/Fut6 and Glg1 are instrumental to the formation of bone metastasis. These findings provide unique insights into the functional role of E-selectin as a component of the vascular niche critical for metastatic colonization in bone. Esposito et al. report a role for bone vascular niche E-selectin in promoting mesenchymal–epithelial Transition and Wnt signalling in breast cancer cells, thereby enhancing bone metastasis.

  • Bone vascular niche E-selectin induces mesenchymal–epithelial Transition and Wnt activation in cancer cells to promote bone metastasis
    Nature cell biology, 2019
    Co-Authors: Mark Esposito, Nandini Mondal, Todd M Greco, Chiara Spadazzi, Hanqiu Zheng, Corey Cheung, Yong Wei, Song Chang Lin, John L. Magnani, Sue Hwa Lin
    Abstract:

    How disseminated tumour cells engage specific stromal components in distant organs for survival and outgrowth is a critical but poorly understood step of the metastatic cascade. Previous studies have demonstrated the importance of the epithelial–mesenchymal Transition in promoting the cancer stem cell properties needed for metastasis initiation, whereas the reverse process of mesenchymal–epithelial Transition is required for metastatic outgrowth. Here we report that this paradoxical requirement for the simultaneous induction of both mesenchymal–epithelial Transition and cancer stem cell traits in disseminated tumour cells is provided by bone vascular niche E-selectin, whose direct binding to cancer cells promotes bone metastasis by inducing mesenchymal–epithelial Transition and activating Wnt signalling. E-selectin binding activity mediated by the α1-3 fucosyltransferases Fut3/Fut6 and Glg1 are instrumental to the formation of bone metastasis. These findings provide unique insights into the functional role of E-selectin as a component of the vascular niche critical for metastatic colonization in bone. Esposito et al. report a role for bone vascular niche E-selectin in promoting mesenchymal–epithelial Transition and Wnt signalling in breast cancer cells, thereby enhancing bone metastasis.

Sheng-chun Wang - One of the best experts on this subject based on the ideXlab platform.

  • Klf4 reduces stemness phenotype, triggers Mesenchymal-Epithelial Transition (MET)-like molecular changes, and prevents tumor progression in nasopharygeal carcinoma
    Oncotarget, 2017
    Co-Authors: Xiqing Li, Zhunlan Zhao, Xiao-ling Zhang, Sheng Yang, Xinglong Yang, Sheng-chun Wang, Wen-tao Zhao
    Abstract:

    // Xiqing Li 1, 2, 3, * , Zhunlan Zhao 1, 3, * , Xiaoling Zhang 4, * , Sheng Yang 1, * , Xia Lin 1 , Xinglong Yang 1 , Xiaolin Lin 1 , Junwen Shi 1 , Shengchun Wang 1 , Wentao Zhao 1 , Jing Li 1 , Fei Gao 1, 7 , Mingyue Liu 3 , Ning Ma 3 , Weiren Luo 8 , Kaitai Yao 1 , Yan Sun 6 , Shengjun Xiao 5 , Dong Xiao 1, 2 and Junshuang Jia 1 1 Guangdong Provincial Key Laboratory of Cancer Immunotherapy Research and Guangzhou Key Laboratory of Tumor Immunology Research, Cancer Research Institute, Southern Medical University, Guangzhou 510515, China 2 Institute of Comparative Medicine & Laboratory Animal Center, Southern Medical University, Guangzhou 510515, China 3 Department of Oncology, The People’s Hosptial of Zhengzhou University, Zhengzhou 450003, China 4 Department of Physiology, Faculty of Basic Medical Sciences, Guilin Medical University, Guilin 541004, China 5 Department of Pathology, The Second Affiliated Hospital, Guilin Medical University, Guilin 541199, China 6 Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou 510080, China 7 Department of Gastroenterology, The First Affiliated Hospital of Jinan University, Guangzhou 510630, China 8 The Third People's Hospital of Shenzhen, Guangdong Medical University, Shenzhen 518112, China * These authors have contributed equally to this work Correspondence to: Dong Xiao, email: xiao_d@hotmail.com Shengjun Xiao, email: xiaoshengjun@glmc.edu.cn Junshuang Jia, email: Jiajsh4@126.com Keywords: Klf4, nasopharyngeal carcinoma (NPC), stemness, epithelial-mesenchymal Transition (EMT), cancer invasion and metastasis Received: March 31, 2017      Accepted: June 29, 2017      Published: September 27, 2017 ABSTRACT The reprogramming factor Kruppel-like factor 4 (Klf4), one of the Yamanaka's reprogramming factors, plays an essential role in reprogramming somatic cells into induced pluripotent stem cells (iPSCs). Klf4 is dysregulated and displays divergent functions in multiple malignancies, but the biological roles of Klf4 in nasopharyngeal carcinoma (NPC) remain unknown. The present study revealed that Klf4 downregulation in a cohort of human NPC biopsies is significantly associated with invasive and metastatic phenotypes of NPC. Our results showed exogenous expression of Klf4 significantly inhibited cell proliferation, decreased stemness, triggered Mesenchymal-Epithelial Transition (MET)-like molecular changes, and suppressed migration and invasion of NPC cells, whereas depletion of endogeneous Klf4 by RNAi reversed the aforementioned biological behaviors and characheristics. Klf4 silencing significantly enhanced the metastatic ability of NPC cells in vivo . In addition, CHIP assay confirmed that E-cadherin is a transcriptional target of Klf4 in NPC cells. Additional studies demonstrated that Klf4-induced MET-like cellular marker alterations, and reduced motility and invasion of NPC cells were mediated by E-cadherin. This study revealed the clinical correlation between Klf4 expression and epithelial-mesenchymal Transition (EMT) biomarkers (including its target gene E-cadherin) in a cohort of NPC biopsies. Taken together, our findings suggest, for what we believe is the first time, that Klf4 functions as a tumor suppressor in NPC to decrease stemness phenotype, inhibit EMT and prevent tumor progression, suggesting that restoring Klf4 function may provide therapeutic benefits in NPC.

  • microrna 122 triggers mesenchymal epithelial Transition and suppresses hepatocellular carcinoma cell motility and invasion by targeting rhoa
    PLOS ONE, 2014
    Co-Authors: Sheng-chun Wang, Sheng Yang, Wen-tao Zhao, Xiaolin Lin, Tingting Zhang, Huiyan Wang, Junwen Shi, Raoying Xie, Fang Wei, Yujuan Qin
    Abstract:

    The loss of microRNA-122 (miR-122) expression is strongly associated with increased invasion and metastasis, and poor prognosis of hepatocellular carcinoma (HCC), however, the underlying mechanisms remain poorly understood. In the present study, we observed that miR-122 over-expression in HCC cell lines Sk-hep-1 and Bel-7402 triggered the Mesenchymal-Epithelial Transition (MET), as demonstrated by epithelial-like morphological changes, up-regulated epithelial proteins (E-cadherin, ZO-1, α-catenin, occludin, BVES, and MST4), and down-regulated mesenchymal proteins (vimentin and fibronectin). The over-expression of miRNA-122 also caused cytoskeleton disruption, RhoA/Rock pathway inactivation, enhanced cell adhesion, and suppression of migration and invasion of Sk-hep-1 and Bel-7402 cells, whereas, these effects could be reversed through miR-122 inhibition. Additional studies demonstrated that the inhibition of wild-type RhoA function induced MET and inhibited cell migration and invasion, while RhoA over-expression reversed miR-122-induced MET and inhibition of migration and invasion of HCC cells, suggesting that miR-122 induced MET and suppressed the migration and invasion of HCC cells by targeting RhoA. Moreover, our results demonstrated that HNF4α up-regulated its target gene miR-122 that subsequently induced MET and inhibited cell migration and invasion, whereas miR-122 inhibition reversed these HNF4α-induced phenotypes. These results revealed functional and mechanistic links among the tumor suppressors HNF4α, miR-122, and RhoA in EMT and invasive and metastatic phenotypes of HCC. Taken together, our study provides the first evidence that the HNF4α/miR-122/RhoA axis negatively regulates EMT and the migration and invasion of HCC cells.

  • The enforced expression of c-Myc in pig fibroblasts triggers Mesenchymal-Epithelial Transition (MET) via F-actin reorganization and RhoA/Rock pathway inactivation.
    Cell cycle (Georgetown Tex.), 2013
    Co-Authors: Junwen Shi, Sheng-chun Wang, Xiaolin Lin, Tingting Zhang, Wei Liu, Junshuang Jia, Hong-fen Sheng, Zhi-fang Yao, Wen-tao Zhao
    Abstract:

    In previous studies from other labs it has been well demonstrated that the ectopic expression of c-Myc in mammary epithelial cells can induce epithelial-mesenchymal Transition (EMT), whereas in our pilot experiment, epithelial-like morphological changes were unexpectedly observed in c-Myc-expressing pig fibroblasts [i.e., porcine embryonic fibroblasts (PEFs) and porcine dermal fibroblasts (PDFs)] and pig mesenchymal stem cells, suggesting that the same c-Myc gene is entitled to trigger EMT in epithelial cells and Mesenchymal-Epithelial Transition (MET) in fibroblasts. This prompted us to characterize the existence of a MET in c-Myc-expressing PEFs and PDFs at the molecular level. qRT-PCR, immunofluorescence and western blot analysis illustrated that epithelial-like morphological changes were accompanied by the increased expression of epithelial markers [such as cell adhesion proteins (E-cadherin, α-catenin and Bves), tight junction protein occludin and cytokeratins (Krt8 and Krt18)], the reduced expression of mesenchymal markers [vimentin, fibronectin 1 (FN1), snail1, collagen family of proteins (COL1A1, COL5A2) and matrix metalloproteinase (MMP) family (MMP12 and MMP14)] and the decreased cell motility and increased cell adhesion in c-Myc-expressing PEFs and PDFs. Furthermore, the ectopic expression of c-Myc in pig fibroblasts disrupted the stress fiber network, suppressed the formation of filopodia and lamellipodia, and resulted in RhoA/Rock pathway inactivation, which finally participates in epithelial-like morphological conversion. Taken together, these findings demonstrate, for the first time, that the enforced expression of c-Myc in fibroblasts can trigger MET, to which cytoskeleton depolymerization and RhoA/Rock pathway inactivation contribute.