12-O-Tetradecanoylphorbol-13-acetate (TPA) is anti-tumorigenic in liver cancer cells via inhibiting YAP through AMOT.
TPA stimulates carcinogenesis in various types of cancers. However, we found that TPA inhibits transformative phenotypes in liver cancer cells via the translocation of YAP from the nucleus, where it functions as a transcriptional co-factor, to the cytoplasm. Such effects led to a separation of YAP from its dependent transcription factors. The inhibitory effects of TPA on YAP were AMOT dependent. Without AMOT, TPA was unable to alter YAP activity. Importantly, the depletion of YAP and AMOT blocked the TPA-reduced transformative phenotypes. In sum, TPA has been established as an anti-tumorigenic drug in liver cancer cells via YAP and AMOT.
Department of Clinical Laboratory, Shanghai Tenth People's Hospital of Tongji University, Shanghai, 200072, China.
Guoqing
G
Zhu
Department of Clinical Laboratory, Shanghai Tenth People's Hospital of Tongji University, Shanghai, 200072, China.
Yan
Y
Chen
Department of Clinical Laboratory, Shanghai Tenth People's Hospital of Tongji University, Shanghai, 200072, China.
Xiao
X
Zhang
Department of Clinical Laboratory, Shanghai Tenth People's Hospital of Tongji University, Shanghai, 200072, China.
Qi
Q
Wu
Department of Clinical Laboratory, Shanghai Tenth People's Hospital of Tongji University, Shanghai, 200072, China.
Yinghui
Y
Zhao
Department of Clinical Laboratory, Shanghai Tenth People's Hospital of Tongji University, Shanghai, 200072, China.
Yuxin
Y
Chen
Department of Clinical Laboratory, Shanghai Tenth People's Hospital of Tongji University, Shanghai, 200072, China.
Fenyong
F
Sun
School of Public Health, Shanghai Jiaotong University School of Medicine, Shanghai, 200025, China.
Yongxia
Y
Qiao
Department of Clinical Laboratory, Shanghai Tenth People's Hospital of Tongji University, Shanghai, 200072, China.|Tongji University Advanced Institute of Translational Medicine, Shanghai, 200092, China.
Jiayi
J
Wang
D000091082:Angiomotins; D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D053148:Caspase 3 / Q000378:metabolism; D053179:Caspase 7 / Q000378:metabolism; D018797:Cell Cycle Proteins; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D002471:Cell Transformation, Neoplastic / Q000235:genetics / Q000378:metabolism; D004195:Disease Models, Animal; D015870:Gene Expression; D064593:Heterografts; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins / Q000235:genetics / Q000378:metabolism*; D008113:Liver Neoplasms / Q000235:genetics / Q000378:metabolism*; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D008840:Microfilament Proteins; D009687:Nuclear Proteins / Q000037:antagonists & inhibitors*; D010641:Phenotype; D021381:Protein Transport; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology*; D014157:Transcription Factors / Q000037:antagonists & inhibitors* / Q000378:metabolism
C423985:AMOT protein, human; D000091082:Angiomotins; D000970:Antineoplastic Agents; D018797:Cell Cycle Proteins; D036341:Intercellular Signaling Peptides and Proteins; D008565:Membrane Proteins; D008840:Microfilament Proteins; D009687:Nuclear Proteins; D014157:Transcription Factors; C456659:YY1AP1 protein, human; D053148:Caspase 3; D053179:Caspase 7; D013755:Tetradecanoylphorbol Acetate