YAP1 induces invadopodia formation by transcriptionally activating TIAM1 through enhancer in breast cancer
Yes-associated protein 1 (YAP1), a central component of the Hippo pathway, plays an important role in tumor metastasis; however, the underlying mechanism remains to be elucidated. Invadopodia are actin-rich protrusions containing multiple proteases and have been widely reported to promote cell invas...
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| Veröffentlicht in: | Oncogene 2022-07, Vol.41 (31), p.3830-3845 |
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| creator | Shen, Jie Huang, Qingwen Jia, Weiyi Feng, Shengjie Liu, Liang Li, Xiaolan Tao, Deding Xie, Daxing |
| description | Yes-associated protein 1 (YAP1), a central component of the Hippo pathway, plays an important role in tumor metastasis; however, the underlying mechanism remains to be elucidated. Invadopodia are actin-rich protrusions containing multiple proteases and have been widely reported to promote cell invasiveness by degrading the extracellular matrix. In the present study, we report that YAP1 induces invadopodia formation and promotes tumor metastasis in breast cancer cells. We also identify TIAM1, a guanine nucleotide exchange factor, as a target of the YAP1–TEAD4 complex. Our results demonstrate that YAP1 could promote TEAD4 binding to the enhancer region of TIAM1, which activates TIAM1 expression, subsequently increasing RAC1 activity and inducing invadopodia formation. These findings reveal the functional role of Hippo signaling in the regulation of invadopodia and provide potential molecular targets for preventing tumor metastasis in breast cancer. |
| doi_str_mv | 10.1038/s41388-022-02344-4 |
| format | Article |
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Invadopodia are actin-rich protrusions containing multiple proteases and have been widely reported to promote cell invasiveness by degrading the extracellular matrix. In the present study, we report that YAP1 induces invadopodia formation and promotes tumor metastasis in breast cancer cells. We also identify TIAM1, a guanine nucleotide exchange factor, as a target of the YAP1–TEAD4 complex. Our results demonstrate that YAP1 could promote TEAD4 binding to the enhancer region of TIAM1, which activates TIAM1 expression, subsequently increasing RAC1 activity and inducing invadopodia formation. These findings reveal the functional role of Hippo signaling in the regulation of invadopodia and provide potential molecular targets for preventing tumor metastasis in breast cancer.</description><identifier>ISSN: 0950-9232</identifier><identifier>EISSN: 1476-5594</identifier><identifier>DOI: 10.1038/s41388-022-02344-4</identifier><identifier>PMID: 35773411</identifier><language>eng</language><publisher>London: Nature Publishing Group UK</publisher><subject>13/1 ; 13/105 ; 13/109 ; 13/51 ; 13/89 ; 14/19 ; 38/39 ; 38/47 ; 631/67/1347 ; 631/67/322 ; 64/60 ; Actin ; Apoptosis ; Breast cancer ; Cell adhesion & migration ; Cell Biology ; Cell growth ; Cloning ; Extracellular matrix ; Gene expression ; Guanine ; Guanine nucleotide exchange factor ; Human Genetics ; Internal Medicine ; Invasiveness ; Kinases ; Lymphatic system ; Medicine ; Medicine & Public Health ; Metastases ; Metastasis ; Oncology ; Proteins ; Rac1 protein ; Tiam1 protein ; Tumors ; Yes-associated protein</subject><ispartof>Oncogene, 2022-07, Vol.41 (31), p.3830-3845</ispartof><rights>The Author(s) 2022</rights><rights>The Author(s) 2022. 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Daxing</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>YAP1 induces invadopodia formation by transcriptionally activating TIAM1 through enhancer in breast cancer</atitle><jtitle>Oncogene</jtitle><stitle>Oncogene</stitle><date>2022-07-29</date><risdate>2022</risdate><volume>41</volume><issue>31</issue><spage>3830</spage><epage>3845</epage><pages>3830-3845</pages><issn>0950-9232</issn><eissn>1476-5594</eissn><abstract>Yes-associated protein 1 (YAP1), a central component of the Hippo pathway, plays an important role in tumor metastasis; however, the underlying mechanism remains to be elucidated. Invadopodia are actin-rich protrusions containing multiple proteases and have been widely reported to promote cell invasiveness by degrading the extracellular matrix. In the present study, we report that YAP1 induces invadopodia formation and promotes tumor metastasis in breast cancer cells. We also identify TIAM1, a guanine nucleotide exchange factor, as a target of the YAP1–TEAD4 complex. Our results demonstrate that YAP1 could promote TEAD4 binding to the enhancer region of TIAM1, which activates TIAM1 expression, subsequently increasing RAC1 activity and inducing invadopodia formation. These findings reveal the functional role of Hippo signaling in the regulation of invadopodia and provide potential molecular targets for preventing tumor metastasis in breast cancer.</abstract><cop>London</cop><pub>Nature Publishing Group UK</pub><pmid>35773411</pmid><doi>10.1038/s41388-022-02344-4</doi><tpages>16</tpages><orcidid>https://orcid.org/0000-0002-3257-2578</orcidid><oa>free_for_read</oa></addata></record> |
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| subjects | 13/1 13/105 13/109 13/51 13/89 14/19 38/39 38/47 631/67/1347 631/67/322 64/60 Actin Apoptosis Breast cancer Cell adhesion & migration Cell Biology Cell growth Cloning Extracellular matrix Gene expression Guanine Guanine nucleotide exchange factor Human Genetics Internal Medicine Invasiveness Kinases Lymphatic system Medicine Medicine & Public Health Metastases Metastasis Oncology Proteins Rac1 protein Tiam1 protein Tumors Yes-associated protein |
| title | YAP1 induces invadopodia formation by transcriptionally activating TIAM1 through enhancer in breast cancer |
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