Twist is a key transcription factor for Epithelial-mesenchymal transition (EMT), which is a cellular de-differentiation program that promotes invasion and metastasis, confers tumor cells with cancer stem cell (CSC)-like characteristics, and increases therapeutic resistance. However, the mechanisms that facilitate the functions of Twist remain unclear. Here we report that Twist overexpression increased expression of PAR1, an upstream regulator of the Hippo pathway; PAR1 promotes invasion, migration, and CSC-like properties in breast cancer by activating the transcriptional co-activator TAZ. Our study indicates that Hippo pathway inhibition is required for the increased migratory and invasiveness ability of breast cancer cells in Twist-mediated EMT.
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This work was supported in part by grants from NIH (RO1s CA125454 and CA188118), DOD Breakthrough Award (BC140733P1), Mary Kay Ash Foundation (to B.P. Zhou), National Natural Science Foundation of China (No. 81402434 to Y. Wang, and No. 81402432 to J. Liu), and the Zhejiang Provincial Natural Science Foundation of China (No. LQ14H280002) (to Y. Wang).
Wang, Yifan; Liu, Jingyi; Ying, Xuhua; Lin, Pengnian Charles; and Zhou, Binhua P., "Twist-mediated Epithelial-mesenchymal Transition Promotes Breast Tumor Cell Invasion via Inhibition of Hippo Pathway" (2016). Molecular and Cellular Biochemistry Faculty Publications. 99.