Twist-mediated Epithelial-mesenchymal Transition Promotes Breast Tumor Cell Invasion via Inhibition of Hippo Pathway

• Published in: Scientific reports Vol. 6; no. 1; p. 24606
• Main Authors: Wang, Yifan, Liu, Jingyi, Ying, Xuhua, Lin, Pengnian Charles, Zhou, Binhua P.
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 20.04.2016; Nature Publishing Group
• Subjects: 13/106; 38/35; 631/67/322; 631/67/395; Apoptosis - genetics; Breast cancer; Breast Neoplasms - genetics; Breast Neoplasms - metabolism; Breast Neoplasms - pathology; Cell Line, Tumor; Cell Movement - genetics; Cell Survival - genetics; Epithelial-Mesenchymal Transition - genetics; Female; Gene Expression; Gene Knockdown Techniques; Humanities and Social Sciences; Humans; Invasiveness; Mesenchyme; Metastases; multidisciplinary; Neoplasm Invasiveness; Protein-Serine-Threonine Kinases - metabolism; Science; Signal Transduction; Snail Family Transcription Factors - genetics; Snail Family Transcription Factors - metabolism; Stem cells; Tumor cells; Twist Transcription Factors - genetics; Twist Transcription Factors - metabolism
• ISSN: 2045-2322; 2045-2322
• DOI: 10.1038/srep24606

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.