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

  • Authors:
    • Guosong Luo
    • Bin Li
    • Chunyan Duan
    • Ying Cheng
    • Bin Xiao
    • Fuli Yao
    • Mei Wei
    • Qinghua Tao
    • Chunhong Feng
    • Xianming Xia
    • Hong Zhou
    • Xiaofang Zhao
    • Rongyang Dai
  • View Affiliations

  • Published online on: August 22, 2017     https://doi.org/10.3892/or.2017.5913
  • Pages: 2498-2506
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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 decreased c‑Myc expression in confluent CCA cells. These results indicate that Merlin/YAP/c‑Myc/mTOR signaling axis promotes human CCA cell proliferation by overriding contact inhibition. We propose that overriding c‑Myc‑mediated contact inhibition is implicated in the development of CCA.
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October-2017
Volume 38 Issue 4

Print ISSN: 1021-335X
Online ISSN:1791-2431

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Spandidos Publications style
Luo G, Li B, Duan C, Cheng Y, Xiao B, Yao F, Wei M, Tao Q, Feng C, Xia X, Xia X, et al: c‑Myc promotes cholangiocarcinoma cells to overcome contact inhibition via the mTOR pathway. Oncol Rep 38: 2498-2506, 2017.
APA
Luo, G., Li, B., Duan, C., Cheng, Y., Xiao, B., Yao, F. ... Dai, R. (2017). c‑Myc promotes cholangiocarcinoma cells to overcome contact inhibition via the mTOR pathway. Oncology Reports, 38, 2498-2506. https://doi.org/10.3892/or.2017.5913
MLA
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."c‑Myc promotes cholangiocarcinoma cells to overcome contact inhibition via the mTOR pathway". Oncology Reports 38.4 (2017): 2498-2506.
Chicago
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."c‑Myc promotes cholangiocarcinoma cells to overcome contact inhibition via the mTOR pathway". Oncology Reports 38, no. 4 (2017): 2498-2506. https://doi.org/10.3892/or.2017.5913