Twist-mediated Epithelial-mesenchymal Transition Promotes Breast Tumor Cell Invasion via Inhibition of Hippo Pathway.
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.
Cancer Institute of Integrative Medicine, Zhejiang Academy of Chinese Medicine, Hangzhou, Zhejiang, 310007, China.|Department of Molecular and Cellular Biochemistry, and Markey Cancer Center, the University of Kentucky, College of Medicine, Lexington, KY 40506, United States.
Yifan
Y
Wang
The State Key Laboratory of Experimental Hematology, Institute of Hematology and Blood Diseases Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Tianjin 300020, China.|Center for Cancer Research, National Cancer Institute-Frederick, Frederick, MD 21702, USA.|Department of Molecular and Cellular Biochemistry, and Markey Cancer Center, the University of Kentucky, College of Medicine, Lexington, KY 40506, United States.
Jingyi
J
Liu
Cancer Institute of Integrative Medicine, Zhejiang Academy of Chinese Medicine, Hangzhou, Zhejiang, 310007, China.
Xuhua
X
Ying
Center for Cancer Research, National Cancer Institute-Frederick, Frederick, MD 21702, USA.
Pengnian Charles
PC
Lin
Department of Molecular and Cellular Biochemistry, and Markey Cancer Center, the University of Kentucky, College of Medicine, Lexington, KY 40506, United States.
Binhua P
BP
Zhou
D017209:Apoptosis / Q000235:genetics; D001943:Breast Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology*; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000235:genetics; D002470:Cell Survival / Q000235:genetics; D058750:Epithelial-Mesenchymal Transition / Q000235:genetics; D005260:Female; D015870:Gene Expression; D055785:Gene Knockdown Techniques; D000090683:Hippo Signaling Pathway; D006801:Humans; D009361:Neoplasm Invasiveness; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism*; D015398:Signal Transduction; D000071250:Snail Family Transcription Factors / Q000235:genetics / Q000378:metabolism; D000071416:Twist Transcription Factors / Q000235:genetics / Q000378:metabolism
D000071250:Snail Family Transcription Factors; D000071416:Twist Transcription Factors; D017346:Protein Serine-Threonine Kinases