YAP1 induces invadopodia formation by transcriptionally activating TIAM1 through enhancer in breast cancer.

Autor: Shen J; Molecular Medicine Center, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, PR China.; Department of GI Surgery, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, PR China., Huang Q; Molecular Medicine Center, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, PR China.; Department of GI Surgery, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, PR China., Jia W; Molecular Medicine Center, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, PR China.; Department of GI Surgery, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, PR China., Feng S; Molecular Medicine Center, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, PR China.; Department of GI Surgery, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, PR China., Liu L; Molecular Medicine Center, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, PR China.; Department of GI Surgery, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, PR China., Li X; Molecular Medicine Center, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, PR China., Tao D; Molecular Medicine Center, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, PR China., Xie D; Molecular Medicine Center, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, PR China. dxxie@tjh.tjmu.edu.cn.; Department of GI Surgery, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, PR China. dxxie@tjh.tjmu.edu.cn.
Jazyk: angličtina
Zdroj: Oncogene [Oncogene] 2022 Jul; Vol. 41 (31), pp. 3830-3845. Date of Electronic Publication: 2022 Jun 30.
DOI: 10.1038/s41388-022-02344-4
Abstrakt: 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.
(© 2022. The Author(s).)
Databáze: MEDLINE
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