c ‑Myc promotes cholangiocarcinoma cells to overcome contact inhibition via the mTOR pathway.

c‑Myc promotes cholangiocarcinoma cells to overcome contact inhibition via the mTOR pathway. Oncol Rep. 2017 Aug 22;: Authors: Luo G, Li B, Duan C, Cheng Y, Xiao B, Yao F, Wei M, Tao Q, Feng C, Xia X, Zhou H, Zhao X, Dai R Abstract The loss of contact inhibition is a hallmark of a wide range of human cancer cells. Yet, the precise mechanism behind this process is not fully understood. c‑Myc plays a pivotal role in carcinogenesis, but its involvement in regulating contact inhibition has not been explored to date. Here, we report that c‑Myc plays an important role in abrogating contact inhibition in human cholangiocarcinoma (CCA) cells. Our data show that the protein level of c‑Myc obviously decreased in contact-inhibited normal biliary epithelial cells. However, CCA cells sustain high protein levels of c‑Myc and keep strong proliferation ability in confluent conditions. Importantly, the suppression of c‑Myc by inhibitor or siRNA induced G0/G1 phase cell cycle arrest in confluent CCA cells. We demonstrate that the inhibition of c‑Myc suppressed the activity of mammalian target of rapamycin (mTOR) in confluent CCA cells, and mTOR inhibition induced G0/G1 phase cell cycle arrest in confluent CCA cells. In confluent CCA cells, the activity of Merlin is downregulated, and Yes-associated protein (YAP) sustains high levels of activity. Furthermore, YAP inhibition not only induced G0/G1 phase cell cycle arrest, but also decrease...
Source: Oncology Reports - Category: Cancer & Oncology Tags: Oncol Rep Source Type: research