TAZ promotes vasculogenic mimicry in gastric cancer through the upregulation of TEAD4
Background and Aim Vasculogenic mimicry (VM) is a unique blood supply pattern in malignant tumors that is closely associated with metastasis and poor prognosis. The Hippo signaling effector TAZ is upregulated in several cancers, promoting cancer proliferation and metastasis. This study aimed to iden...
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| Veröffentlicht in: | Journal of gastroenterology and hepatology 2022-04, Vol.37 (4), p.714-726 |
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| container_title | Journal of gastroenterology and hepatology |
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| creator | Zhang, Yanhui Bai, Jingru Cheng, Runfen Zhang, Danfang Qiu, Zhiqiang Liu, Tieju Che, Na Dong, Xueyi Zhao, Nan Lin, Xian Liang, Xiaohui Li, Fan Li, Yue Sun, Baocun Zhao, Xiulan |
| description | Background and Aim
Vasculogenic mimicry (VM) is a unique blood supply pattern in malignant tumors that is closely associated with metastasis and poor prognosis. The Hippo signaling effector TAZ is upregulated in several cancers, promoting cancer proliferation and metastasis. This study aimed to identify the function of TAZ and its regulatory mechanism in promoting VM in gastric cancer (GC).
Methods
The expression of TAZ and TEAD4 and their correlations with overall survival and VM‐related markers were analyzed in 228 cases of GC. The regulatory mechanism of TAZ and its interaction with TEAD4 in epithelial‐mesenchymal transition (EMT) and VM were investigated in vitro and in vivo.
Results
TAZ was highly expressed in GC samples and was associated with shorter patient survival time. TAZ expression was positively correlated with TEAD4 and VM in patients with GC. TAZ enhanced the migration and invasion capacity of GC cells through EMT in vitro and upregulated the expression of VM‐associated proteins, including VE‐cadherin, MMP2, and MMP9, thus promoting VM formation. Overexpression of TAZ accelerated the growth of subcutaneous xenograft and promoted VM formation in vivo. Co‐immunoprecipitation assays showed that TAZ can directly bind to TEAD4, and in vitro experiments showed that this binding mediates the function of TAZ in regulating EMT and VM formation in GC.
Conclusions
TAZ promotes GC metastasis and VM by upregulating TEAD4 expression. Our findings expand the role of TAZ in VM and provide new theoretical support for the use of antiangiogenic therapy in the treatment of advanced GC. |
| doi_str_mv | 10.1111/jgh.15779 |
| format | Article |
| fullrecord | <record><control><sourceid>proquest_cross</sourceid><recordid>TN_cdi_proquest_miscellaneous_2622288246</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><sourcerecordid>2622288246</sourcerecordid><originalsourceid>FETCH-LOGICAL-c3539-a202287fc4e06aabd11a80d53da2c43c0dc4716f401c05e63ce190afab5292333</originalsourceid><addsrcrecordid>eNp10E9PwjAYBvDGaATRg1_ANPGih8HbP-u2I0EEDYkXuHhZSteNkW3FdtPw7a2CHkzs5U2aX572fRC6JjAk_oy2xWZIwihKTlCfcA4Bibg4RX2ISRgkjCQ9dOHcFgA4ROE56rEQBAVO-2i1HL_inTW1abXD79KprjKFbkqF67Iuld3jssGFdK31V0o2Slvcbqzpio2fGnc7q4uukm1pGmxyvJyOH_glOstl5fTVcQ7Q6nG6nMyDxcvsaTJeBIqFLAkkBUrjKFdcg5BynREiY8hClkmqOFOQKR4RkXMgCkItmNIkAZnLdUgTyhgboLtDrt_grdOuTevSKV1VstGmcykV1D8QUy48vf1Dt6azjf-dV1zEkYgoeHV_UMoa56zO050ta2n3KYH0q-vUd51-d-3tzTGxW9c6-5U_5XowOoCPstL7_5PS59n8EPkJNvGHEA</addsrcrecordid><sourcetype>Aggregation Database</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>2646876720</pqid></control><display><type>article</type><title>TAZ promotes vasculogenic mimicry in gastric cancer through the upregulation of TEAD4</title><source>MEDLINE</source><source>Wiley Online Library Journals Frontfile Complete</source><creator>Zhang, Yanhui ; Bai, Jingru ; Cheng, Runfen ; Zhang, Danfang ; Qiu, Zhiqiang ; Liu, Tieju ; Che, Na ; Dong, Xueyi ; Zhao, Nan ; Lin, Xian ; Liang, Xiaohui ; Li, Fan ; Li, Yue ; Sun, Baocun ; Zhao, Xiulan</creator><creatorcontrib>Zhang, Yanhui ; Bai, Jingru ; Cheng, Runfen ; Zhang, Danfang ; Qiu, Zhiqiang ; Liu, Tieju ; Che, Na ; Dong, Xueyi ; Zhao, Nan ; Lin, Xian ; Liang, Xiaohui ; Li, Fan ; Li, Yue ; Sun, Baocun ; Zhao, Xiulan</creatorcontrib><description>Background and Aim
Vasculogenic mimicry (VM) is a unique blood supply pattern in malignant tumors that is closely associated with metastasis and poor prognosis. The Hippo signaling effector TAZ is upregulated in several cancers, promoting cancer proliferation and metastasis. This study aimed to identify the function of TAZ and its regulatory mechanism in promoting VM in gastric cancer (GC).
Methods
The expression of TAZ and TEAD4 and their correlations with overall survival and VM‐related markers were analyzed in 228 cases of GC. The regulatory mechanism of TAZ and its interaction with TEAD4 in epithelial‐mesenchymal transition (EMT) and VM were investigated in vitro and in vivo.
Results
TAZ was highly expressed in GC samples and was associated with shorter patient survival time. TAZ expression was positively correlated with TEAD4 and VM in patients with GC. TAZ enhanced the migration and invasion capacity of GC cells through EMT in vitro and upregulated the expression of VM‐associated proteins, including VE‐cadherin, MMP2, and MMP9, thus promoting VM formation. Overexpression of TAZ accelerated the growth of subcutaneous xenograft and promoted VM formation in vivo. Co‐immunoprecipitation assays showed that TAZ can directly bind to TEAD4, and in vitro experiments showed that this binding mediates the function of TAZ in regulating EMT and VM formation in GC.
Conclusions
TAZ promotes GC metastasis and VM by upregulating TEAD4 expression. Our findings expand the role of TAZ in VM and provide new theoretical support for the use of antiangiogenic therapy in the treatment of advanced GC.</description><identifier>ISSN: 0815-9319</identifier><identifier>EISSN: 1440-1746</identifier><identifier>DOI: 10.1111/jgh.15779</identifier><identifier>PMID: 35062042</identifier><language>eng</language><publisher>Australia: Wiley Subscription Services, Inc</publisher><subject>Cadherins ; Cell Line, Tumor ; DNA-Binding Proteins - genetics ; Epithelial-Mesenchymal Transition - genetics ; epithelial‐mesenchymal transition ; Gastric cancer ; Gelatinase A ; Gelatinase B ; Gene Expression Regulation, Neoplastic ; Humans ; Immunoprecipitation ; Medical prognosis ; Mesenchyme ; Metastases ; Metastasis ; Mimicry ; Muscle Proteins - genetics ; Muscle Proteins - metabolism ; Neovascularization, Pathologic - genetics ; Neovascularization, Pathologic - pathology ; Patients ; Stomach Neoplasms - pathology ; TAZ ; TEA Domain Transcription Factors - genetics ; TEAD4 ; Transcriptional Coactivator with PDZ-Binding Motif Proteins - genetics ; Tumors ; Up-Regulation ; vasculogenic mimicry ; Xenografts</subject><ispartof>Journal of gastroenterology and hepatology, 2022-04, Vol.37 (4), p.714-726</ispartof><rights>2022 Journal of Gastroenterology and Hepatology Foundation and John Wiley & Sons Australia, Ltd</rights><rights>2022 Journal of Gastroenterology and Hepatology Foundation and John Wiley & Sons Australia, Ltd.</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c3539-a202287fc4e06aabd11a80d53da2c43c0dc4716f401c05e63ce190afab5292333</citedby><cites>FETCH-LOGICAL-c3539-a202287fc4e06aabd11a80d53da2c43c0dc4716f401c05e63ce190afab5292333</cites><orcidid>0000-0002-9314-2854</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://onlinelibrary.wiley.com/doi/pdf/10.1111%2Fjgh.15779$$EPDF$$P50$$Gwiley$$H</linktopdf><linktohtml>$$Uhttps://onlinelibrary.wiley.com/doi/full/10.1111%2Fjgh.15779$$EHTML$$P50$$Gwiley$$H</linktohtml><link.rule.ids>314,776,780,1411,27903,27904,45553,45554</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/35062042$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Zhang, Yanhui</creatorcontrib><creatorcontrib>Bai, Jingru</creatorcontrib><creatorcontrib>Cheng, Runfen</creatorcontrib><creatorcontrib>Zhang, Danfang</creatorcontrib><creatorcontrib>Qiu, Zhiqiang</creatorcontrib><creatorcontrib>Liu, Tieju</creatorcontrib><creatorcontrib>Che, Na</creatorcontrib><creatorcontrib>Dong, Xueyi</creatorcontrib><creatorcontrib>Zhao, Nan</creatorcontrib><creatorcontrib>Lin, Xian</creatorcontrib><creatorcontrib>Liang, Xiaohui</creatorcontrib><creatorcontrib>Li, Fan</creatorcontrib><creatorcontrib>Li, Yue</creatorcontrib><creatorcontrib>Sun, Baocun</creatorcontrib><creatorcontrib>Zhao, Xiulan</creatorcontrib><title>TAZ promotes vasculogenic mimicry in gastric cancer through the upregulation of TEAD4</title><title>Journal of gastroenterology and hepatology</title><addtitle>J Gastroenterol Hepatol</addtitle><description>Background and Aim
Vasculogenic mimicry (VM) is a unique blood supply pattern in malignant tumors that is closely associated with metastasis and poor prognosis. The Hippo signaling effector TAZ is upregulated in several cancers, promoting cancer proliferation and metastasis. This study aimed to identify the function of TAZ and its regulatory mechanism in promoting VM in gastric cancer (GC).
Methods
The expression of TAZ and TEAD4 and their correlations with overall survival and VM‐related markers were analyzed in 228 cases of GC. The regulatory mechanism of TAZ and its interaction with TEAD4 in epithelial‐mesenchymal transition (EMT) and VM were investigated in vitro and in vivo.
Results
TAZ was highly expressed in GC samples and was associated with shorter patient survival time. TAZ expression was positively correlated with TEAD4 and VM in patients with GC. TAZ enhanced the migration and invasion capacity of GC cells through EMT in vitro and upregulated the expression of VM‐associated proteins, including VE‐cadherin, MMP2, and MMP9, thus promoting VM formation. Overexpression of TAZ accelerated the growth of subcutaneous xenograft and promoted VM formation in vivo. Co‐immunoprecipitation assays showed that TAZ can directly bind to TEAD4, and in vitro experiments showed that this binding mediates the function of TAZ in regulating EMT and VM formation in GC.
Conclusions
TAZ promotes GC metastasis and VM by upregulating TEAD4 expression. Our findings expand the role of TAZ in VM and provide new theoretical support for the use of antiangiogenic therapy in the treatment of advanced GC.</description><subject>Cadherins</subject><subject>Cell Line, Tumor</subject><subject>DNA-Binding Proteins - genetics</subject><subject>Epithelial-Mesenchymal Transition - genetics</subject><subject>epithelial‐mesenchymal transition</subject><subject>Gastric cancer</subject><subject>Gelatinase A</subject><subject>Gelatinase B</subject><subject>Gene Expression Regulation, Neoplastic</subject><subject>Humans</subject><subject>Immunoprecipitation</subject><subject>Medical prognosis</subject><subject>Mesenchyme</subject><subject>Metastases</subject><subject>Metastasis</subject><subject>Mimicry</subject><subject>Muscle Proteins - genetics</subject><subject>Muscle Proteins - metabolism</subject><subject>Neovascularization, Pathologic - genetics</subject><subject>Neovascularization, Pathologic - pathology</subject><subject>Patients</subject><subject>Stomach Neoplasms - pathology</subject><subject>TAZ</subject><subject>TEA Domain Transcription Factors - genetics</subject><subject>TEAD4</subject><subject>Transcriptional Coactivator with PDZ-Binding Motif Proteins - genetics</subject><subject>Tumors</subject><subject>Up-Regulation</subject><subject>vasculogenic mimicry</subject><subject>Xenografts</subject><issn>0815-9319</issn><issn>1440-1746</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2022</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp10E9PwjAYBvDGaATRg1_ANPGih8HbP-u2I0EEDYkXuHhZSteNkW3FdtPw7a2CHkzs5U2aX572fRC6JjAk_oy2xWZIwihKTlCfcA4Bibg4RX2ISRgkjCQ9dOHcFgA4ROE56rEQBAVO-2i1HL_inTW1abXD79KprjKFbkqF67Iuld3jssGFdK31V0o2Slvcbqzpio2fGnc7q4uukm1pGmxyvJyOH_glOstl5fTVcQ7Q6nG6nMyDxcvsaTJeBIqFLAkkBUrjKFdcg5BynREiY8hClkmqOFOQKR4RkXMgCkItmNIkAZnLdUgTyhgboLtDrt_grdOuTevSKV1VstGmcykV1D8QUy48vf1Dt6azjf-dV1zEkYgoeHV_UMoa56zO050ta2n3KYH0q-vUd51-d-3tzTGxW9c6-5U_5XowOoCPstL7_5PS59n8EPkJNvGHEA</recordid><startdate>202204</startdate><enddate>202204</enddate><creator>Zhang, Yanhui</creator><creator>Bai, Jingru</creator><creator>Cheng, Runfen</creator><creator>Zhang, Danfang</creator><creator>Qiu, Zhiqiang</creator><creator>Liu, Tieju</creator><creator>Che, Na</creator><creator>Dong, Xueyi</creator><creator>Zhao, Nan</creator><creator>Lin, Xian</creator><creator>Liang, Xiaohui</creator><creator>Li, Fan</creator><creator>Li, Yue</creator><creator>Sun, Baocun</creator><creator>Zhao, Xiulan</creator><general>Wiley Subscription Services, Inc</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7T5</scope><scope>7U9</scope><scope>H94</scope><scope>7X8</scope><orcidid>https://orcid.org/0000-0002-9314-2854</orcidid></search><sort><creationdate>202204</creationdate><title>TAZ promotes vasculogenic mimicry in gastric cancer through the upregulation of TEAD4</title><author>Zhang, Yanhui ; Bai, Jingru ; Cheng, Runfen ; Zhang, Danfang ; Qiu, Zhiqiang ; Liu, Tieju ; Che, Na ; Dong, Xueyi ; Zhao, Nan ; Lin, Xian ; Liang, Xiaohui ; Li, Fan ; Li, Yue ; Sun, Baocun ; Zhao, Xiulan</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c3539-a202287fc4e06aabd11a80d53da2c43c0dc4716f401c05e63ce190afab5292333</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2022</creationdate><topic>Cadherins</topic><topic>Cell Line, Tumor</topic><topic>DNA-Binding Proteins - genetics</topic><topic>Epithelial-Mesenchymal Transition - genetics</topic><topic>epithelial‐mesenchymal transition</topic><topic>Gastric cancer</topic><topic>Gelatinase A</topic><topic>Gelatinase B</topic><topic>Gene Expression Regulation, Neoplastic</topic><topic>Humans</topic><topic>Immunoprecipitation</topic><topic>Medical prognosis</topic><topic>Mesenchyme</topic><topic>Metastases</topic><topic>Metastasis</topic><topic>Mimicry</topic><topic>Muscle Proteins - genetics</topic><topic>Muscle Proteins - metabolism</topic><topic>Neovascularization, Pathologic - genetics</topic><topic>Neovascularization, Pathologic - pathology</topic><topic>Patients</topic><topic>Stomach Neoplasms - pathology</topic><topic>TAZ</topic><topic>TEA Domain Transcription Factors - genetics</topic><topic>TEAD4</topic><topic>Transcriptional Coactivator with PDZ-Binding Motif Proteins - genetics</topic><topic>Tumors</topic><topic>Up-Regulation</topic><topic>vasculogenic mimicry</topic><topic>Xenografts</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Zhang, Yanhui</creatorcontrib><creatorcontrib>Bai, Jingru</creatorcontrib><creatorcontrib>Cheng, Runfen</creatorcontrib><creatorcontrib>Zhang, Danfang</creatorcontrib><creatorcontrib>Qiu, Zhiqiang</creatorcontrib><creatorcontrib>Liu, Tieju</creatorcontrib><creatorcontrib>Che, Na</creatorcontrib><creatorcontrib>Dong, Xueyi</creatorcontrib><creatorcontrib>Zhao, Nan</creatorcontrib><creatorcontrib>Lin, Xian</creatorcontrib><creatorcontrib>Liang, Xiaohui</creatorcontrib><creatorcontrib>Li, Fan</creatorcontrib><creatorcontrib>Li, Yue</creatorcontrib><creatorcontrib>Sun, Baocun</creatorcontrib><creatorcontrib>Zhao, Xiulan</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Immunology Abstracts</collection><collection>Virology and AIDS Abstracts</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>MEDLINE - Academic</collection><jtitle>Journal of gastroenterology and hepatology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Zhang, Yanhui</au><au>Bai, Jingru</au><au>Cheng, Runfen</au><au>Zhang, Danfang</au><au>Qiu, Zhiqiang</au><au>Liu, Tieju</au><au>Che, Na</au><au>Dong, Xueyi</au><au>Zhao, Nan</au><au>Lin, Xian</au><au>Liang, Xiaohui</au><au>Li, Fan</au><au>Li, Yue</au><au>Sun, Baocun</au><au>Zhao, Xiulan</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>TAZ promotes vasculogenic mimicry in gastric cancer through the upregulation of TEAD4</atitle><jtitle>Journal of gastroenterology and hepatology</jtitle><addtitle>J Gastroenterol Hepatol</addtitle><date>2022-04</date><risdate>2022</risdate><volume>37</volume><issue>4</issue><spage>714</spage><epage>726</epage><pages>714-726</pages><issn>0815-9319</issn><eissn>1440-1746</eissn><abstract>Background and Aim
Vasculogenic mimicry (VM) is a unique blood supply pattern in malignant tumors that is closely associated with metastasis and poor prognosis. The Hippo signaling effector TAZ is upregulated in several cancers, promoting cancer proliferation and metastasis. This study aimed to identify the function of TAZ and its regulatory mechanism in promoting VM in gastric cancer (GC).
Methods
The expression of TAZ and TEAD4 and their correlations with overall survival and VM‐related markers were analyzed in 228 cases of GC. The regulatory mechanism of TAZ and its interaction with TEAD4 in epithelial‐mesenchymal transition (EMT) and VM were investigated in vitro and in vivo.
Results
TAZ was highly expressed in GC samples and was associated with shorter patient survival time. TAZ expression was positively correlated with TEAD4 and VM in patients with GC. TAZ enhanced the migration and invasion capacity of GC cells through EMT in vitro and upregulated the expression of VM‐associated proteins, including VE‐cadherin, MMP2, and MMP9, thus promoting VM formation. Overexpression of TAZ accelerated the growth of subcutaneous xenograft and promoted VM formation in vivo. Co‐immunoprecipitation assays showed that TAZ can directly bind to TEAD4, and in vitro experiments showed that this binding mediates the function of TAZ in regulating EMT and VM formation in GC.
Conclusions
TAZ promotes GC metastasis and VM by upregulating TEAD4 expression. Our findings expand the role of TAZ in VM and provide new theoretical support for the use of antiangiogenic therapy in the treatment of advanced GC.</abstract><cop>Australia</cop><pub>Wiley Subscription Services, Inc</pub><pmid>35062042</pmid><doi>10.1111/jgh.15779</doi><tpages>13</tpages><orcidid>https://orcid.org/0000-0002-9314-2854</orcidid></addata></record> |
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| subjects | Cadherins Cell Line, Tumor DNA-Binding Proteins - genetics Epithelial-Mesenchymal Transition - genetics epithelial‐mesenchymal transition Gastric cancer Gelatinase A Gelatinase B Gene Expression Regulation, Neoplastic Humans Immunoprecipitation Medical prognosis Mesenchyme Metastases Metastasis Mimicry Muscle Proteins - genetics Muscle Proteins - metabolism Neovascularization, Pathologic - genetics Neovascularization, Pathologic - pathology Patients Stomach Neoplasms - pathology TAZ TEA Domain Transcription Factors - genetics TEAD4 Transcriptional Coactivator with PDZ-Binding Motif Proteins - genetics Tumors Up-Regulation vasculogenic mimicry Xenografts |
| title | TAZ promotes vasculogenic mimicry in gastric cancer through the upregulation of TEAD4 |
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