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E3 ubiquitin ligase FBW7α inhibits cholangiocarcinoma cell proliferation by downregulating c-Myc and cyclin E

Ming Li1, Ling Ouyang2, Zhigang Zheng3

  • 1Department of Hepatobiliary Pancreas and Vessel Surgery, Chenggong Hospital of Xiamen University, Xiamen, Fujian, P.R. China.

Oncology Reports
|February 11, 2017
PubMed

Insights

F-box and WD repeat domain-containing 7 (FBW7) acts as a tumor suppressor in cholangiocarcinoma (CCA) by inhibiting cell proliferation. Targeting its substrate c-Myc may offer a new therapeutic strategy for CCA treatment.

Area of Science:

  • Oncology
  • Molecular Biology
  • Biochemistry

Background:

  • F-box and WD repeat domain-containing 7 (FBW7) is a crucial tumor suppressor targeting oncoproteins for degradation.
  • FBW7 mutations are common in human cancers, but its role in cholangiocarcinoma (CCA) is not well understood.

Purpose of the Study:

  • To investigate the function of FBW7 in cholangiocarcinoma (CCA) cell proliferation and tumor growth.
  • To identify FBW7 targets involved in CCA progression.

Main Methods:

  • Overexpression of FBW7α in CCA cells.
  • Assessment of cell cycle progression and proliferation in vitro.
  • Evaluation of CCA xenograft tumor growth in vivo.
  • Analysis of c-Myc and cyclin E protein levels.

Main Results:

  • FBW7α overexpression induced G1 cell cycle arrest and inhibited CCA cell proliferation and xenograft tumor growth.
  • FBW7α overexpression led to the degradation of c-Myc and cyclin E.
  • Restoring c-Myc, but not cyclin E, rescued proliferation in FBW7α-overexpressing CCA cells.

Conclusions:

  • FBW7α functions as a tumor suppressor in CCA progression.
  • FBW7α inhibits CCA by degrading c-Myc and cyclin E.
  • Targeting FBW7α substrate c-Myc presents a potential therapeutic strategy for CCA.

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