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.
基金:
National Natural Science Foundation of China [81572861, 81773053]
第一作者单位:[1]Huazhong Univ Sci & Technol, Tongji Hosp, Tongji Med Coll, Mol Med Ctr, Wuhan, Peoples R China[2]Huazhong Univ Sci & Technol, Tongji Hosp, Dept GI Surg, Tongji Med Coll, Wuhan, Peoples R China
通讯作者:
通讯机构:[1]Huazhong Univ Sci & Technol, Tongji Hosp, Tongji Med Coll, Mol Med Ctr, Wuhan, Peoples R China[2]Huazhong Univ Sci & Technol, Tongji Hosp, Dept GI Surg, Tongji Med Coll, Wuhan, Peoples R China
推荐引用方式(GB/T 7714):
Shen Jie,Huang Qingwen,Jia Weiyi,et al.YAP1 induces invadopodia formation by transcriptionally activating TIAM1 through enhancer in breast cancer[J].ONCOGENE.2022,41(31):3830-3845.doi:10.1038/s41388-022-02344-4.
APA:
Shen, Jie,Huang, Qingwen,Jia, Weiyi,Feng, Shengjie,Liu, Liang...&Xie, Daxing.(2022).YAP1 induces invadopodia formation by transcriptionally activating TIAM1 through enhancer in breast cancer.ONCOGENE,41,(31)
MLA:
Shen, Jie,et al."YAP1 induces invadopodia formation by transcriptionally activating TIAM1 through enhancer in breast cancer".ONCOGENE 41..31(2022):3830-3845