Increased TEAD4 expression and nuclear localization in colorectal cancer promote epithelial–mesenchymal transition and metastasis in a YAP-independent manner
Dysregulation of the Hippo pathway occurs in a variety of cancers and often correlates with a poor prognosis. To further explore the potential role of Hippo pathway dysregulation in tumor development and progression, we investigated its downstream transcription factor TEAD4 in colorectal cancer (CRC...
Gespeichert in:
| Veröffentlicht in: | Oncogene 2016-05, Vol.35 (21), p.2789-2800 |
|---|---|
| Hauptverfasser: | , , , , , , , , |
| Format: | Artikel |
| Sprache: | eng |
| Schlagworte: | |
| Online-Zugang: | Volltext |
| Tags: |
Tag hinzufügen
Keine Tags, Fügen Sie den ersten Tag hinzu!
|
| container_end_page | 2800 |
|---|---|
| container_issue | 21 |
| container_start_page | 2789 |
| container_title | Oncogene |
| container_volume | 35 |
| creator | Liu, Y Wang, G Yang, Y Mei, Z Liang, Z Cui, A Wu, T Liu, C-Y Cui, L |
| description | Dysregulation of the Hippo pathway occurs in a variety of cancers and often correlates with a poor prognosis. To further explore the potential role of Hippo pathway dysregulation in tumor development and progression, we investigated its downstream transcription factor TEAD4 in colorectal cancer (CRC). Increased expression and nuclear localization of TEAD4 were found in a significant portion of CRC tissues, in association with metastasis and a poor prognosis. In CRC cells, TEAD4 knockdown induced the mesenchymal–epithelial transition and decreased cell mobility
in vitro
and metastasis
in vivo
. Microarray analysis revealed that TEAD4 promoted cell adhesion and upregulated the epithelial–mesenchymal transition-related transcriptome in CRC cells. Vimentin was identified as a new direct target gene mediating TEAD4 function in CRC cells, whereby forced vimentin expression markedly reversed TEAD4-knockdown-induced cell morphological changes and decreased mobility. Interestingly, rescued expression of both WT TEAD4 and a Y429H mutant can reverse the mesenchymal–epithelial transition and increase vimentin expression, cell mobility and metastatic potential in TEAD4-knockdown CRC cells. The discrepant expression of YAP and TEAD4 in CRC tissues, the rescue ability of TEAD4 mutant defect in YAP binding and no effect on vimentin expression by YAP knockdown in CRC cells, all implicated a YAP-independent manner of TEAD4 function in CRC. Furthermore, vimentin positively correlated and CDH1 reversely correlated with the level of TEAD4 in CRC tissues and xenograft tumors. Our results suggest that TEAD4 nuclear expression can serve as a biomarker for CRC progression and poor prognosis. The transcription factor TEAD4 regulates a pro-metastasis transcription program in a YAP-independent manner in CRC, thus providing a novel mechanism of TEAD4 transcriptional regulation and its oncogenic role in CRC, independently of the Hippo pathway. |
| doi_str_mv | 10.1038/onc.2015.342 |
| format | Article |
| fullrecord | <record><control><sourceid>gale_proqu</sourceid><recordid>TN_cdi_proquest_miscellaneous_1808741418</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><galeid>A458571886</galeid><sourcerecordid>A458571886</sourcerecordid><originalsourceid>FETCH-LOGICAL-c589t-fdf088b9de48c7df93d39bcda70951d3d2efc0c779a21b0ca8b16f4064a31fec3</originalsourceid><addsrcrecordid>eNqFks9uFSEUxidGY6_VnWtD4saFc4WBGZjlTa3apIku6sIVYeBMS8PACExiXfkOPoDv5pPI5Lb-S6OBcBLO73xwTr6qekzwlmAqXgSvtw0m7Zay5k61IYx3ddv27G61wX2L676hzUH1IKVLjDHvcXO_Omg6KnhLxab6duJ1BJXAoLPj3UuG4NMcISUbPFLeIL9oByoiF7Ry9rPKa8J6pIMLEXRWDmnlNUQ0xzCFDAhmmy_AWeW-f_k6QQKvL66mwuWofLL5RnmCrFLZNq16Cn3YvautNzBDOXxGk_Ie4sPq3qhcgkfX8bB6_-r47OhNffr29cnR7rTWrehzPZoRCzH0BpjQ3Iw9NbQftFG8zIAYahoYNdac96ohA9ZKDKQbGe6YomQETQ-rZ3vd0sbHBVKWk00anFMewpIkEVhwRhgR_0d5GTmnLe4L-vQv9DIs0ZdGZNMx0ooWC_wvatXigjLGflHnyoG0fgxloHp9Wu5YUeJEiK5Q21uosgxMVgcPoy33fxQ83xfoGFKKMMo52knFK0mwXA0mi8HkajBZDFbwJ9d_XYYJzE_4xlEFqPdAKil_DvG3Zm4T_AEY29xr</addsrcrecordid><sourcetype>Aggregation Database</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>1792783444</pqid></control><display><type>article</type><title>Increased TEAD4 expression and nuclear localization in colorectal cancer promote epithelial–mesenchymal transition and metastasis in a YAP-independent manner</title><source>MEDLINE</source><source>SpringerLink Journals</source><source>Nature Journals Online</source><creator>Liu, Y ; Wang, G ; Yang, Y ; Mei, Z ; Liang, Z ; Cui, A ; Wu, T ; Liu, C-Y ; Cui, L</creator><creatorcontrib>Liu, Y ; Wang, G ; Yang, Y ; Mei, Z ; Liang, Z ; Cui, A ; Wu, T ; Liu, C-Y ; Cui, L</creatorcontrib><description>Dysregulation of the Hippo pathway occurs in a variety of cancers and often correlates with a poor prognosis. To further explore the potential role of Hippo pathway dysregulation in tumor development and progression, we investigated its downstream transcription factor TEAD4 in colorectal cancer (CRC). Increased expression and nuclear localization of TEAD4 were found in a significant portion of CRC tissues, in association with metastasis and a poor prognosis. In CRC cells, TEAD4 knockdown induced the mesenchymal–epithelial transition and decreased cell mobility
in vitro
and metastasis
in vivo
. Microarray analysis revealed that TEAD4 promoted cell adhesion and upregulated the epithelial–mesenchymal transition-related transcriptome in CRC cells. Vimentin was identified as a new direct target gene mediating TEAD4 function in CRC cells, whereby forced vimentin expression markedly reversed TEAD4-knockdown-induced cell morphological changes and decreased mobility. Interestingly, rescued expression of both WT TEAD4 and a Y429H mutant can reverse the mesenchymal–epithelial transition and increase vimentin expression, cell mobility and metastatic potential in TEAD4-knockdown CRC cells. The discrepant expression of YAP and TEAD4 in CRC tissues, the rescue ability of TEAD4 mutant defect in YAP binding and no effect on vimentin expression by YAP knockdown in CRC cells, all implicated a YAP-independent manner of TEAD4 function in CRC. Furthermore, vimentin positively correlated and CDH1 reversely correlated with the level of TEAD4 in CRC tissues and xenograft tumors. Our results suggest that TEAD4 nuclear expression can serve as a biomarker for CRC progression and poor prognosis. The transcription factor TEAD4 regulates a pro-metastasis transcription program in a YAP-independent manner in CRC, thus providing a novel mechanism of TEAD4 transcriptional regulation and its oncogenic role in CRC, independently of the Hippo pathway.</description><identifier>ISSN: 0950-9232</identifier><identifier>EISSN: 1476-5594</identifier><identifier>DOI: 10.1038/onc.2015.342</identifier><identifier>PMID: 26387538</identifier><identifier>CODEN: ONCNES</identifier><language>eng</language><publisher>London: Nature Publishing Group UK</publisher><subject>631/67 ; 631/80 ; Adaptor Proteins, Signal Transducing - metabolism ; Animals ; Apoptosis ; Apoptosis - physiology ; Cell adhesion ; Cell Biology ; Cell Line, Tumor ; Cell Nucleus - metabolism ; Cell Proliferation - physiology ; Cellular signal transduction ; Colorectal cancer ; Colorectal carcinoma ; Colorectal Neoplasms - metabolism ; Colorectal Neoplasms - pathology ; Development and progression ; DNA microarrays ; DNA-Binding Proteins - biosynthesis ; DNA-Binding Proteins - metabolism ; E-cadherin ; Epithelial-Mesenchymal Transition ; Gene expression ; Gene regulation ; Genetic aspects ; Health aspects ; Heterografts ; Human Genetics ; Humans ; Internal Medicine ; Localization ; Male ; Medical prognosis ; Medicine ; Medicine & Public Health ; Mesenchyme ; Metastases ; Metastasis ; Mice ; Mice, Nude ; Mobility ; Muscle Proteins - biosynthesis ; Muscle Proteins - metabolism ; Mutants ; Neoplasm Metastasis ; Oncology ; original-article ; Phosphoproteins - metabolism ; Prognosis ; Properties ; Protein-Serine-Threonine Kinases - metabolism ; Transcription factors ; Transcription Factors - biosynthesis ; Transcription Factors - metabolism ; Transcriptional Activation ; Transcriptomes ; Transfection ; Tumor proteins ; Tumors ; Vimentin ; Xenografts ; Yes-associated protein</subject><ispartof>Oncogene, 2016-05, Vol.35 (21), p.2789-2800</ispartof><rights>Macmillan Publishers Limited 2016</rights><rights>COPYRIGHT 2016 Nature Publishing Group</rights><rights>Copyright Nature Publishing Group May 26, 2016</rights><rights>Macmillan Publishers Limited 2016.</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c589t-fdf088b9de48c7df93d39bcda70951d3d2efc0c779a21b0ca8b16f4064a31fec3</citedby><cites>FETCH-LOGICAL-c589t-fdf088b9de48c7df93d39bcda70951d3d2efc0c779a21b0ca8b16f4064a31fec3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://link.springer.com/content/pdf/10.1038/onc.2015.342$$EPDF$$P50$$Gspringer$$H</linktopdf><linktohtml>$$Uhttps://link.springer.com/10.1038/onc.2015.342$$EHTML$$P50$$Gspringer$$H</linktohtml><link.rule.ids>314,776,780,27901,27902,41464,42533,51294</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/26387538$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Liu, Y</creatorcontrib><creatorcontrib>Wang, G</creatorcontrib><creatorcontrib>Yang, Y</creatorcontrib><creatorcontrib>Mei, Z</creatorcontrib><creatorcontrib>Liang, Z</creatorcontrib><creatorcontrib>Cui, A</creatorcontrib><creatorcontrib>Wu, T</creatorcontrib><creatorcontrib>Liu, C-Y</creatorcontrib><creatorcontrib>Cui, L</creatorcontrib><title>Increased TEAD4 expression and nuclear localization in colorectal cancer promote epithelial–mesenchymal transition and metastasis in a YAP-independent manner</title><title>Oncogene</title><addtitle>Oncogene</addtitle><addtitle>Oncogene</addtitle><description>Dysregulation of the Hippo pathway occurs in a variety of cancers and often correlates with a poor prognosis. To further explore the potential role of Hippo pathway dysregulation in tumor development and progression, we investigated its downstream transcription factor TEAD4 in colorectal cancer (CRC). Increased expression and nuclear localization of TEAD4 were found in a significant portion of CRC tissues, in association with metastasis and a poor prognosis. In CRC cells, TEAD4 knockdown induced the mesenchymal–epithelial transition and decreased cell mobility
in vitro
and metastasis
in vivo
. Microarray analysis revealed that TEAD4 promoted cell adhesion and upregulated the epithelial–mesenchymal transition-related transcriptome in CRC cells. Vimentin was identified as a new direct target gene mediating TEAD4 function in CRC cells, whereby forced vimentin expression markedly reversed TEAD4-knockdown-induced cell morphological changes and decreased mobility. Interestingly, rescued expression of both WT TEAD4 and a Y429H mutant can reverse the mesenchymal–epithelial transition and increase vimentin expression, cell mobility and metastatic potential in TEAD4-knockdown CRC cells. The discrepant expression of YAP and TEAD4 in CRC tissues, the rescue ability of TEAD4 mutant defect in YAP binding and no effect on vimentin expression by YAP knockdown in CRC cells, all implicated a YAP-independent manner of TEAD4 function in CRC. Furthermore, vimentin positively correlated and CDH1 reversely correlated with the level of TEAD4 in CRC tissues and xenograft tumors. Our results suggest that TEAD4 nuclear expression can serve as a biomarker for CRC progression and poor prognosis. The transcription factor TEAD4 regulates a pro-metastasis transcription program in a YAP-independent manner in CRC, thus providing a novel mechanism of TEAD4 transcriptional regulation and its oncogenic role in CRC, independently of the Hippo pathway.</description><subject>631/67</subject><subject>631/80</subject><subject>Adaptor Proteins, Signal Transducing - metabolism</subject><subject>Animals</subject><subject>Apoptosis</subject><subject>Apoptosis - physiology</subject><subject>Cell adhesion</subject><subject>Cell Biology</subject><subject>Cell Line, Tumor</subject><subject>Cell Nucleus - metabolism</subject><subject>Cell Proliferation - physiology</subject><subject>Cellular signal transduction</subject><subject>Colorectal cancer</subject><subject>Colorectal carcinoma</subject><subject>Colorectal Neoplasms - metabolism</subject><subject>Colorectal Neoplasms - pathology</subject><subject>Development and progression</subject><subject>DNA microarrays</subject><subject>DNA-Binding Proteins - biosynthesis</subject><subject>DNA-Binding Proteins - metabolism</subject><subject>E-cadherin</subject><subject>Epithelial-Mesenchymal Transition</subject><subject>Gene expression</subject><subject>Gene regulation</subject><subject>Genetic aspects</subject><subject>Health aspects</subject><subject>Heterografts</subject><subject>Human Genetics</subject><subject>Humans</subject><subject>Internal Medicine</subject><subject>Localization</subject><subject>Male</subject><subject>Medical prognosis</subject><subject>Medicine</subject><subject>Medicine & Public Health</subject><subject>Mesenchyme</subject><subject>Metastases</subject><subject>Metastasis</subject><subject>Mice</subject><subject>Mice, Nude</subject><subject>Mobility</subject><subject>Muscle Proteins - biosynthesis</subject><subject>Muscle Proteins - metabolism</subject><subject>Mutants</subject><subject>Neoplasm Metastasis</subject><subject>Oncology</subject><subject>original-article</subject><subject>Phosphoproteins - metabolism</subject><subject>Prognosis</subject><subject>Properties</subject><subject>Protein-Serine-Threonine Kinases - metabolism</subject><subject>Transcription factors</subject><subject>Transcription Factors - biosynthesis</subject><subject>Transcription Factors - metabolism</subject><subject>Transcriptional Activation</subject><subject>Transcriptomes</subject><subject>Transfection</subject><subject>Tumor proteins</subject><subject>Tumors</subject><subject>Vimentin</subject><subject>Xenografts</subject><subject>Yes-associated protein</subject><issn>0950-9232</issn><issn>1476-5594</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2016</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><sourceid>8G5</sourceid><sourceid>BENPR</sourceid><sourceid>GUQSH</sourceid><sourceid>M2O</sourceid><recordid>eNqFks9uFSEUxidGY6_VnWtD4saFc4WBGZjlTa3apIku6sIVYeBMS8PACExiXfkOPoDv5pPI5Lb-S6OBcBLO73xwTr6qekzwlmAqXgSvtw0m7Zay5k61IYx3ddv27G61wX2L676hzUH1IKVLjDHvcXO_Omg6KnhLxab6duJ1BJXAoLPj3UuG4NMcISUbPFLeIL9oByoiF7Ry9rPKa8J6pIMLEXRWDmnlNUQ0xzCFDAhmmy_AWeW-f_k6QQKvL66mwuWofLL5RnmCrFLZNq16Cn3YvautNzBDOXxGk_Ie4sPq3qhcgkfX8bB6_-r47OhNffr29cnR7rTWrehzPZoRCzH0BpjQ3Iw9NbQftFG8zIAYahoYNdac96ohA9ZKDKQbGe6YomQETQ-rZ3vd0sbHBVKWk00anFMewpIkEVhwRhgR_0d5GTmnLe4L-vQv9DIs0ZdGZNMx0ooWC_wvatXigjLGflHnyoG0fgxloHp9Wu5YUeJEiK5Q21uosgxMVgcPoy33fxQ83xfoGFKKMMo52knFK0mwXA0mi8HkajBZDFbwJ9d_XYYJzE_4xlEFqPdAKil_DvG3Zm4T_AEY29xr</recordid><startdate>20160501</startdate><enddate>20160501</enddate><creator>Liu, Y</creator><creator>Wang, G</creator><creator>Yang, Y</creator><creator>Mei, Z</creator><creator>Liang, Z</creator><creator>Cui, A</creator><creator>Wu, T</creator><creator>Liu, C-Y</creator><creator>Cui, L</creator><general>Nature Publishing Group UK</general><general>Nature Publishing Group</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>3V.</scope><scope>7TM</scope><scope>7TO</scope><scope>7U9</scope><scope>7X7</scope><scope>7XB</scope><scope>88A</scope><scope>88E</scope><scope>8AO</scope><scope>8C1</scope><scope>8FD</scope><scope>8FE</scope><scope>8FH</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>8G5</scope><scope>ABUWG</scope><scope>AFKRA</scope><scope>AZQEC</scope><scope>BBNVY</scope><scope>BENPR</scope><scope>BHPHI</scope><scope>CCPQU</scope><scope>DWQXO</scope><scope>FR3</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>GNUQQ</scope><scope>GUQSH</scope><scope>H94</scope><scope>HCIFZ</scope><scope>K9.</scope><scope>LK8</scope><scope>M0S</scope><scope>M1P</scope><scope>M2O</scope><scope>M7P</scope><scope>MBDVC</scope><scope>P64</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PRINS</scope><scope>Q9U</scope><scope>RC3</scope><scope>7X8</scope></search><sort><creationdate>20160501</creationdate><title>Increased TEAD4 expression and nuclear localization in colorectal cancer promote epithelial–mesenchymal transition and metastasis in a YAP-independent manner</title><author>Liu, Y ; Wang, G ; Yang, Y ; Mei, Z ; Liang, Z ; Cui, A ; Wu, T ; Liu, C-Y ; Cui, L</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c589t-fdf088b9de48c7df93d39bcda70951d3d2efc0c779a21b0ca8b16f4064a31fec3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2016</creationdate><topic>631/67</topic><topic>631/80</topic><topic>Adaptor Proteins, Signal Transducing - metabolism</topic><topic>Animals</topic><topic>Apoptosis</topic><topic>Apoptosis - physiology</topic><topic>Cell adhesion</topic><topic>Cell Biology</topic><topic>Cell Line, Tumor</topic><topic>Cell Nucleus - metabolism</topic><topic>Cell Proliferation - physiology</topic><topic>Cellular signal transduction</topic><topic>Colorectal cancer</topic><topic>Colorectal carcinoma</topic><topic>Colorectal Neoplasms - metabolism</topic><topic>Colorectal Neoplasms - pathology</topic><topic>Development and progression</topic><topic>DNA microarrays</topic><topic>DNA-Binding Proteins - biosynthesis</topic><topic>DNA-Binding Proteins - metabolism</topic><topic>E-cadherin</topic><topic>Epithelial-Mesenchymal Transition</topic><topic>Gene expression</topic><topic>Gene regulation</topic><topic>Genetic aspects</topic><topic>Health aspects</topic><topic>Heterografts</topic><topic>Human Genetics</topic><topic>Humans</topic><topic>Internal Medicine</topic><topic>Localization</topic><topic>Male</topic><topic>Medical prognosis</topic><topic>Medicine</topic><topic>Medicine & Public Health</topic><topic>Mesenchyme</topic><topic>Metastases</topic><topic>Metastasis</topic><topic>Mice</topic><topic>Mice, Nude</topic><topic>Mobility</topic><topic>Muscle Proteins - biosynthesis</topic><topic>Muscle Proteins - metabolism</topic><topic>Mutants</topic><topic>Neoplasm Metastasis</topic><topic>Oncology</topic><topic>original-article</topic><topic>Phosphoproteins - metabolism</topic><topic>Prognosis</topic><topic>Properties</topic><topic>Protein-Serine-Threonine Kinases - metabolism</topic><topic>Transcription factors</topic><topic>Transcription Factors - biosynthesis</topic><topic>Transcription Factors - metabolism</topic><topic>Transcriptional Activation</topic><topic>Transcriptomes</topic><topic>Transfection</topic><topic>Tumor proteins</topic><topic>Tumors</topic><topic>Vimentin</topic><topic>Xenografts</topic><topic>Yes-associated protein</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Liu, Y</creatorcontrib><creatorcontrib>Wang, G</creatorcontrib><creatorcontrib>Yang, Y</creatorcontrib><creatorcontrib>Mei, Z</creatorcontrib><creatorcontrib>Liang, Z</creatorcontrib><creatorcontrib>Cui, A</creatorcontrib><creatorcontrib>Wu, T</creatorcontrib><creatorcontrib>Liu, C-Y</creatorcontrib><creatorcontrib>Cui, L</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>ProQuest Central (Corporate)</collection><collection>Nucleic Acids Abstracts</collection><collection>Oncogenes and Growth Factors Abstracts</collection><collection>Virology and AIDS Abstracts</collection><collection>Health & Medical Collection</collection><collection>ProQuest Central (purchase pre-March 2016)</collection><collection>Biology Database (Alumni Edition)</collection><collection>Medical Database (Alumni Edition)</collection><collection>ProQuest Pharma Collection</collection><collection>Public Health Database</collection><collection>Technology Research Database</collection><collection>ProQuest SciTech Collection</collection><collection>ProQuest Natural Science Collection</collection><collection>Hospital Premium Collection</collection><collection>Hospital Premium Collection (Alumni Edition)</collection><collection>ProQuest Central (Alumni) (purchase pre-March 2016)</collection><collection>Research Library (Alumni Edition)</collection><collection>ProQuest Central (Alumni Edition)</collection><collection>ProQuest Central UK/Ireland</collection><collection>ProQuest Central Essentials</collection><collection>Biological Science Collection</collection><collection>ProQuest Central</collection><collection>Natural Science Collection</collection><collection>ProQuest One Community College</collection><collection>ProQuest Central Korea</collection><collection>Engineering Research Database</collection><collection>Health Research Premium Collection</collection><collection>Health Research Premium Collection (Alumni)</collection><collection>ProQuest Central Student</collection><collection>Research Library Prep</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>SciTech Premium Collection</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>ProQuest Biological Science Collection</collection><collection>Health & Medical Collection (Alumni Edition)</collection><collection>Medical Database</collection><collection>Research Library</collection><collection>Biological Science Database</collection><collection>Research Library (Corporate)</collection><collection>Biotechnology and BioEngineering Abstracts</collection><collection>ProQuest One Academic Eastern Edition (DO NOT USE)</collection><collection>ProQuest One Academic</collection><collection>ProQuest One Academic UKI Edition</collection><collection>ProQuest Central China</collection><collection>ProQuest Central Basic</collection><collection>Genetics Abstracts</collection><collection>MEDLINE - Academic</collection><jtitle>Oncogene</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Liu, Y</au><au>Wang, G</au><au>Yang, Y</au><au>Mei, Z</au><au>Liang, Z</au><au>Cui, A</au><au>Wu, T</au><au>Liu, C-Y</au><au>Cui, L</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Increased TEAD4 expression and nuclear localization in colorectal cancer promote epithelial–mesenchymal transition and metastasis in a YAP-independent manner</atitle><jtitle>Oncogene</jtitle><stitle>Oncogene</stitle><addtitle>Oncogene</addtitle><date>2016-05-01</date><risdate>2016</risdate><volume>35</volume><issue>21</issue><spage>2789</spage><epage>2800</epage><pages>2789-2800</pages><issn>0950-9232</issn><eissn>1476-5594</eissn><coden>ONCNES</coden><abstract>Dysregulation of the Hippo pathway occurs in a variety of cancers and often correlates with a poor prognosis. To further explore the potential role of Hippo pathway dysregulation in tumor development and progression, we investigated its downstream transcription factor TEAD4 in colorectal cancer (CRC). Increased expression and nuclear localization of TEAD4 were found in a significant portion of CRC tissues, in association with metastasis and a poor prognosis. In CRC cells, TEAD4 knockdown induced the mesenchymal–epithelial transition and decreased cell mobility
in vitro
and metastasis
in vivo
. Microarray analysis revealed that TEAD4 promoted cell adhesion and upregulated the epithelial–mesenchymal transition-related transcriptome in CRC cells. Vimentin was identified as a new direct target gene mediating TEAD4 function in CRC cells, whereby forced vimentin expression markedly reversed TEAD4-knockdown-induced cell morphological changes and decreased mobility. Interestingly, rescued expression of both WT TEAD4 and a Y429H mutant can reverse the mesenchymal–epithelial transition and increase vimentin expression, cell mobility and metastatic potential in TEAD4-knockdown CRC cells. The discrepant expression of YAP and TEAD4 in CRC tissues, the rescue ability of TEAD4 mutant defect in YAP binding and no effect on vimentin expression by YAP knockdown in CRC cells, all implicated a YAP-independent manner of TEAD4 function in CRC. Furthermore, vimentin positively correlated and CDH1 reversely correlated with the level of TEAD4 in CRC tissues and xenograft tumors. Our results suggest that TEAD4 nuclear expression can serve as a biomarker for CRC progression and poor prognosis. The transcription factor TEAD4 regulates a pro-metastasis transcription program in a YAP-independent manner in CRC, thus providing a novel mechanism of TEAD4 transcriptional regulation and its oncogenic role in CRC, independently of the Hippo pathway.</abstract><cop>London</cop><pub>Nature Publishing Group UK</pub><pmid>26387538</pmid><doi>10.1038/onc.2015.342</doi><tpages>12</tpages><oa>free_for_read</oa></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 0950-9232 |
| ispartof | Oncogene, 2016-05, Vol.35 (21), p.2789-2800 |
| issn | 0950-9232 1476-5594 |
| language | eng |
| recordid | cdi_proquest_miscellaneous_1808741418 |
| source | MEDLINE; SpringerLink Journals; Nature Journals Online |
| subjects | 631/67 631/80 Adaptor Proteins, Signal Transducing - metabolism Animals Apoptosis Apoptosis - physiology Cell adhesion Cell Biology Cell Line, Tumor Cell Nucleus - metabolism Cell Proliferation - physiology Cellular signal transduction Colorectal cancer Colorectal carcinoma Colorectal Neoplasms - metabolism Colorectal Neoplasms - pathology Development and progression DNA microarrays DNA-Binding Proteins - biosynthesis DNA-Binding Proteins - metabolism E-cadherin Epithelial-Mesenchymal Transition Gene expression Gene regulation Genetic aspects Health aspects Heterografts Human Genetics Humans Internal Medicine Localization Male Medical prognosis Medicine Medicine & Public Health Mesenchyme Metastases Metastasis Mice Mice, Nude Mobility Muscle Proteins - biosynthesis Muscle Proteins - metabolism Mutants Neoplasm Metastasis Oncology original-article Phosphoproteins - metabolism Prognosis Properties Protein-Serine-Threonine Kinases - metabolism Transcription factors Transcription Factors - biosynthesis Transcription Factors - metabolism Transcriptional Activation Transcriptomes Transfection Tumor proteins Tumors Vimentin Xenografts Yes-associated protein |
| title | Increased TEAD4 expression and nuclear localization in colorectal cancer promote epithelial–mesenchymal transition and metastasis in a YAP-independent manner |
| url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2025-02-08T15%3A12%3A50IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-gale_proqu&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=Increased%20TEAD4%20expression%20and%20nuclear%20localization%20in%20colorectal%20cancer%20promote%20epithelial%E2%80%93mesenchymal%20transition%20and%20metastasis%20in%20a%20YAP-independent%20manner&rft.jtitle=Oncogene&rft.au=Liu,%20Y&rft.date=2016-05-01&rft.volume=35&rft.issue=21&rft.spage=2789&rft.epage=2800&rft.pages=2789-2800&rft.issn=0950-9232&rft.eissn=1476-5594&rft.coden=ONCNES&rft_id=info:doi/10.1038/onc.2015.342&rft_dat=%3Cgale_proqu%3EA458571886%3C/gale_proqu%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_pqid=1792783444&rft_id=info:pmid/26387538&rft_galeid=A458571886&rfr_iscdi=true |