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FBW7 suppresses ovarian cancer development by targeting the N6-methyladenosine binding protein YTHDF2

Fei Xu1,2, Jiajia Li1,2, Mengdong Ni1,2

  • 1Department of Gynecologic Oncology, Fudan University Shanghai Cancer Center, Fudan University, Shanghai, 200032, China.

Molecular Cancer
|March 4, 2021
PubMed
Abstract

Insights

The tumor suppressor FBW7 inhibits ovarian cancer progression by targeting YTHDF2 for degradation. This mechanism suppresses YTHDF2-mediated decay of the pro-apoptotic gene BMF, thereby reducing tumor growth.

Area of Science:

  • Oncology
  • Molecular Biology
  • Biochemistry

Background:

  • FBW7 is a tumor suppressor that targets oncogenic proteins for degradation.
  • Its role in ovarian cancer progression is not well understood.

Purpose of the Study:

  • To investigate the function of FBW7 in ovarian cancer.
  • To identify substrates and mechanisms of FBW7 action in this disease.

Main Methods:

  • Immunoprecipitation-Mass Spectrometry (IP-MASS) and co-immunoprecipitation (co-IP) to identify FBW7 substrates.
  • In vitro and in vivo models to assess FBW7's biological effects.
  • LC/MS, MeRIP-Seq, and RNA-Seq to analyze m6A modification levels and downstream targets.

Main Results:

  • FBW7 is downregulated in ovarian cancer, with high expression correlating with better prognosis and elevated m6A levels.
  • FBW7 inhibits ovarian cancer cell survival and proliferation.
  • YTHDF2 is a novel FBW7 substrate, and FBW7 induces its proteasomal degradation, counteracting YTHDF2's tumor-promoting effects.

Conclusions:

  • FBW7 suppresses ovarian cancer growth by antagonizing YTHDF2-mediated BMF mRNA decay.
  • This highlights a novel mechanism of tumor suppression involving FBW7 and m6A pathway regulation.
Keywords:
BMFFBW7N6-methyladenosineUbiquitinationYTHDF2

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