ZEB1‐mediated vasculogenic mimicry formation associates with epithelial–mesenchymal transition and cancer stem cell phenotypes in prostate cancer
The zinc finger E‐box‐binding homeobox 1 (ZEB1) induced the epithelial–mesenchymal transition (EMT) and altered ZEB1 expression could lead to aggressive and cancer stem cell (CSC) phenotypes in various cancers. Tissue specimens from 96 prostate cancer patients were collected for immunohistochemistry...
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| Veröffentlicht in: | Journal of cellular and molecular medicine 2018-08, Vol.22 (8), p.3768-3781 |
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| creator | Wang, Hua Huang, Bin Li, Bai Mou Cao, Kai Yuan Mo, Chen Qiang Jiang, Shuang Jian Pan, Jin Cheng Wang, Zong Ren Lin, Huan Yi Wang, Dao Hu Qiu, Shao Peng |
| description | The zinc finger E‐box‐binding homeobox 1 (ZEB1) induced the epithelial–mesenchymal transition (EMT) and altered ZEB1 expression could lead to aggressive and cancer stem cell (CSC) phenotypes in various cancers. Tissue specimens from 96 prostate cancer patients were collected for immunohistochemistry and CD34/periodic acid–Schiff double staining. Prostate cancer cells were subjected to ZEB1 knockdown or overexpression and assessment of the effects on vasculogenic mimicry formation in vitro and in vivo. The underlying molecular events of ZEB1‐induced vasculogenic mimicry formation in prostate cancer were then explored. The data showed that the presence of VM and high ZEB1 expression was associated with higher Gleason score, TNM stage, and lymph node and distant metastases as well as with the expression of vimentin and CD133 in prostate cancer tissues. Furthermore, ZEB1 was required for VM formation and altered expression of EMT‐related and CSC‐associated proteins in prostate cancer cells in vitro and in vivo. ZEB1 also facilitated tumour cell migration, invasion and clonogenicity. In addition, the effects of ZEB1 in prostate cancer cells were mediated by Src signalling; that is PP2, a specific inhibitor of the Src signalling, dose dependently reduced the p‐Src527 level but not p‐Src416 level, while ZEB1 knockdown also down‐regulated the level of p‐Src527 in PC3 and DU‐145 cells. PP2 treatment also significantly reduced the expression of VE‐cadherin, vimentin and CD133 in these prostate cancer cells. Src signalling mediated the effects of ZEB1 on VM formation and gene expression. |
| doi_str_mv | 10.1111/jcmm.13637 |
| format | Article |
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Tissue specimens from 96 prostate cancer patients were collected for immunohistochemistry and CD34/periodic acid–Schiff double staining. Prostate cancer cells were subjected to ZEB1 knockdown or overexpression and assessment of the effects on vasculogenic mimicry formation in vitro and in vivo. The underlying molecular events of ZEB1‐induced vasculogenic mimicry formation in prostate cancer were then explored. The data showed that the presence of VM and high ZEB1 expression was associated with higher Gleason score, TNM stage, and lymph node and distant metastases as well as with the expression of vimentin and CD133 in prostate cancer tissues. Furthermore, ZEB1 was required for VM formation and altered expression of EMT‐related and CSC‐associated proteins in prostate cancer cells in vitro and in vivo. ZEB1 also facilitated tumour cell migration, invasion and clonogenicity. In addition, the effects of ZEB1 in prostate cancer cells were mediated by Src signalling; that is PP2, a specific inhibitor of the Src signalling, dose dependently reduced the p‐Src527 level but not p‐Src416 level, while ZEB1 knockdown also down‐regulated the level of p‐Src527 in PC3 and DU‐145 cells. PP2 treatment also significantly reduced the expression of VE‐cadherin, vimentin and CD133 in these prostate cancer cells. Src signalling mediated the effects of ZEB1 on VM formation and gene expression.</description><identifier>ISSN: 1582-1838</identifier><identifier>EISSN: 1582-4934</identifier><identifier>DOI: 10.1111/jcmm.13637</identifier><identifier>PMID: 29754422</identifier><language>eng</language><publisher>England: John Wiley & Sons, Inc</publisher><subject>Cadherins ; CD34 antigen ; Cell adhesion & migration ; Cell migration ; CSC ; EMT ; Gene expression ; Homeobox ; Immunohistochemistry ; Lymph nodes ; Mesenchyme ; Metastases ; Mimicry ; Molecular chains ; Original ; Phenotypes ; Prostate cancer ; Proteins ; Stem cells ; Tumors ; vasculogenic mimicry ; Vimentin ; ZEB1 ; Zinc ; Zinc finger proteins</subject><ispartof>Journal of cellular and molecular medicine, 2018-08, Vol.22 (8), p.3768-3781</ispartof><rights>2018 The Authors. Journal of Cellular and Molecular Medicine published by John Wiley & Sons Ltd and Foundation for Cellular and Molecular Medicine.</rights><rights>2018. This work is published under http://creativecommons.org/licenses/by/4.0/ (the “License”). 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Tissue specimens from 96 prostate cancer patients were collected for immunohistochemistry and CD34/periodic acid–Schiff double staining. Prostate cancer cells were subjected to ZEB1 knockdown or overexpression and assessment of the effects on vasculogenic mimicry formation in vitro and in vivo. The underlying molecular events of ZEB1‐induced vasculogenic mimicry formation in prostate cancer were then explored. The data showed that the presence of VM and high ZEB1 expression was associated with higher Gleason score, TNM stage, and lymph node and distant metastases as well as with the expression of vimentin and CD133 in prostate cancer tissues. Furthermore, ZEB1 was required for VM formation and altered expression of EMT‐related and CSC‐associated proteins in prostate cancer cells in vitro and in vivo. ZEB1 also facilitated tumour cell migration, invasion and clonogenicity. In addition, the effects of ZEB1 in prostate cancer cells were mediated by Src signalling; that is PP2, a specific inhibitor of the Src signalling, dose dependently reduced the p‐Src527 level but not p‐Src416 level, while ZEB1 knockdown also down‐regulated the level of p‐Src527 in PC3 and DU‐145 cells. PP2 treatment also significantly reduced the expression of VE‐cadherin, vimentin and CD133 in these prostate cancer cells. Src signalling mediated the effects of ZEB1 on VM formation and gene expression.</description><subject>Cadherins</subject><subject>CD34 antigen</subject><subject>Cell adhesion & migration</subject><subject>Cell migration</subject><subject>CSC</subject><subject>EMT</subject><subject>Gene expression</subject><subject>Homeobox</subject><subject>Immunohistochemistry</subject><subject>Lymph nodes</subject><subject>Mesenchyme</subject><subject>Metastases</subject><subject>Mimicry</subject><subject>Molecular chains</subject><subject>Original</subject><subject>Phenotypes</subject><subject>Prostate cancer</subject><subject>Proteins</subject><subject>Stem cells</subject><subject>Tumors</subject><subject>vasculogenic mimicry</subject><subject>Vimentin</subject><subject>ZEB1</subject><subject>Zinc</subject><subject>Zinc finger 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vasculogenic mimicry formation associates with epithelial–mesenchymal transition and cancer stem cell phenotypes in prostate cancer</title><author>Wang, Hua ; Huang, Bin ; Li, Bai Mou ; Cao, Kai Yuan ; Mo, Chen Qiang ; Jiang, Shuang Jian ; Pan, Jin Cheng ; Wang, Zong Ren ; Lin, Huan Yi ; Wang, Dao Hu ; Qiu, Shao Peng</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-p3367-8fd7b58bc1872aa6fcabd5470bc6b8da867bc1c22d497dfcada44af24b81653f3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2018</creationdate><topic>Cadherins</topic><topic>CD34 antigen</topic><topic>Cell adhesion & migration</topic><topic>Cell migration</topic><topic>CSC</topic><topic>EMT</topic><topic>Gene expression</topic><topic>Homeobox</topic><topic>Immunohistochemistry</topic><topic>Lymph nodes</topic><topic>Mesenchyme</topic><topic>Metastases</topic><topic>Mimicry</topic><topic>Molecular 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Peng</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>ZEB1‐mediated vasculogenic mimicry formation associates with epithelial–mesenchymal transition and cancer stem cell phenotypes in prostate cancer</atitle><jtitle>Journal of cellular and molecular medicine</jtitle><addtitle>J Cell Mol Med</addtitle><date>2018-08</date><risdate>2018</risdate><volume>22</volume><issue>8</issue><spage>3768</spage><epage>3781</epage><pages>3768-3781</pages><issn>1582-1838</issn><eissn>1582-4934</eissn><abstract>The zinc finger E‐box‐binding homeobox 1 (ZEB1) induced the epithelial–mesenchymal transition (EMT) and altered ZEB1 expression could lead to aggressive and cancer stem cell (CSC) phenotypes in various cancers. Tissue specimens from 96 prostate cancer patients were collected for immunohistochemistry and CD34/periodic acid–Schiff double staining. Prostate cancer cells were subjected to ZEB1 knockdown or overexpression and assessment of the effects on vasculogenic mimicry formation in vitro and in vivo. The underlying molecular events of ZEB1‐induced vasculogenic mimicry formation in prostate cancer were then explored. The data showed that the presence of VM and high ZEB1 expression was associated with higher Gleason score, TNM stage, and lymph node and distant metastases as well as with the expression of vimentin and CD133 in prostate cancer tissues. Furthermore, ZEB1 was required for VM formation and altered expression of EMT‐related and CSC‐associated proteins in prostate cancer cells in vitro and in vivo. ZEB1 also facilitated tumour cell migration, invasion and clonogenicity. In addition, the effects of ZEB1 in prostate cancer cells were mediated by Src signalling; that is PP2, a specific inhibitor of the Src signalling, dose dependently reduced the p‐Src527 level but not p‐Src416 level, while ZEB1 knockdown also down‐regulated the level of p‐Src527 in PC3 and DU‐145 cells. PP2 treatment also significantly reduced the expression of VE‐cadherin, vimentin and CD133 in these prostate cancer cells. Src signalling mediated the effects of ZEB1 on VM formation and gene expression.</abstract><cop>England</cop><pub>John Wiley & Sons, Inc</pub><pmid>29754422</pmid><doi>10.1111/jcmm.13637</doi><tpages>14</tpages><orcidid>https://orcid.org/0000-0003-3084-4717</orcidid><oa>free_for_read</oa></addata></record> |
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| subjects | Cadherins CD34 antigen Cell adhesion & migration Cell migration CSC EMT Gene expression Homeobox Immunohistochemistry Lymph nodes Mesenchyme Metastases Mimicry Molecular chains Original Phenotypes Prostate cancer Proteins Stem cells Tumors vasculogenic mimicry Vimentin ZEB1 Zinc Zinc finger proteins |
| title | ZEB1‐mediated vasculogenic mimicry formation associates with epithelial–mesenchymal transition and cancer stem cell phenotypes in prostate cancer |
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