The Role of FBXW7 in Gynecologic Malignancies

Cells. 2023 May 17;12(10):1415. doi: 10.3390/cells12101415.

Abstract

The F-Box and WD Repeat Domain Containing 7 (FBXW7) protein has been shown to regulate cellular growth and act as a tumor suppressor. This protein, also known as FBW7, hCDC4, SEL10 or hAGO, is encoded by the gene FBXW7. It is a crucial component of the Skp1-Cullin1-F-box (SCF) complex, which is a ubiquitin ligase. This complex aids in the degradation of many oncoproteins, such as cyclin E, c-JUN, c-MYC, NOTCH, and MCL1, via the ubiquitin-proteasome system (UPS). The FBXW7 gene is commonly mutated or deleted in numerous types of cancer, including gynecologic cancers (GCs). Such FBXW7 mutations are linked to a poor prognosis due to increased treatment resistance. Hence, detection of the FBXW7 mutation may possibly be an appropriate diagnostic and prognostic biomarker that plays a central role in determining suitable individualized management. Recent studies also suggest that, under specific circumstances, FBXW7 may act as an oncogene. There is mounting evidence indicating that the aberrant expression of FBXW7 is involved in the development of GCs. The aim of this review is to give an update on the role of FBXW7 as a potential biomarker and also as a therapeutic target for novel treatments, particularly in the management of GCs.

Keywords: FBXW7; LncRNAs; epigenetic; gynecologic cancers; miRNAs; mutations; target therapy; ubiquitin-proteasome system.

Publication types

  • Review
  • Research Support, Non-U.S. Gov't

MeSH terms

  • F-Box Proteins* / genetics
  • F-Box Proteins* / metabolism
  • F-Box-WD Repeat-Containing Protein 7 / genetics
  • F-Box-WD Repeat-Containing Protein 7 / metabolism
  • Female
  • Genital Neoplasms, Female* / genetics
  • Humans
  • Ubiquitin-Protein Ligases / genetics
  • Ubiquitin-Protein Ligases / metabolism
  • Ubiquitins / metabolism

Substances

  • F-Box-WD Repeat-Containing Protein 7
  • F-Box Proteins
  • Ubiquitin-Protein Ligases
  • Ubiquitins
  • FBXW7 protein, human

Grants and funding

This paper is based upon work from COST Action CA18117—European network for Gynaecological Rare Cancer research: From Concept to Cure (GYNOCARE), supported by the European Co-operation in Science and Technology (COST). COST is a funding agency for research and innovation networks. COST actions help connect research initiatives across Europe and enable scientists to grow their ideas by sharing them with their peers. This boosts their research, careers, and innovation (www.cost.eu accessed on 24 April 2023). R.D.F., S.S. (Sherif Suleiman), R.D.-F., Y.S., M.V.-S., A.Y., F.P., A.G., and J.C.-A. are action management committee members and/or form part of Working Groups 1–5, and J.C.-A. is the chairperson of this action.