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Review
. 2022 Mar 26;21(1):87.
doi: 10.1186/s12943-022-01548-2.

Clinical significance of FBXW7 loss of function in human cancers

Jingyi Fan  1   2   3 , Marcia Bellon  4 , Mingyi Ju  2   3 , Lin Zhao  2   3 , Minjie Wei  2   3 , Liwu Fu  5 , Christophe Nicot  6
Affiliations
Review

Clinical significance of FBXW7 loss of function in human cancers

Jingyi Fan et al. Mol Cancer. .

Abstract

FBXW7 (F-Box and WD Repeat Domain Containing 7) (also referred to as FBW7 or hCDC4) is a component of the Skp1-Cdc53 / Cullin-F-box-protein complex (SCF/β-TrCP). As a member of the F-box protein family, FBXW7 serves a role in phosphorylation-dependent ubiquitination and proteasome degradation of oncoproteins that play critical role(s) in oncogenesis. FBXW7 affects many regulatory functions involved in cell survival, cell proliferation, tumor invasion, DNA damage repair, genomic instability and telomere biology. This thorough review of current literature details how FBXW7 expression and functions are regulated through multiple mechanisms and how that ultimately drives tumorigenesis in a wide array of cell types. The clinical significance of FBXW7 is highlighted by the fact that FBXW7 is frequently inactivated in human lung, colon, and hematopoietic cancers. The loss of FBXW7 can serve as an independent prognostic marker and is significantly correlated with the resistance of tumor cells to chemotherapeutic agents and poorer disease outcomes. Recent evidence shows that genetic mutation of FBXW7 differentially affects the degradation of specific cellular targets resulting in a distinct and specific pattern of activation/inactivation of cell signaling pathways. The clinical significance of FBXW7 mutations in the context of tumor development, progression, and resistance to therapies as well as opportunities for targeted therapies is discussed.

Keywords: Aneuploidy; Apoptosis; CDC4; Cancer; Cell cycle; Centrosome; Chromosome instability; Cyclin E; DNA repair; Drug resistance; Epigenetic; FBW7; FBXW7; Immunotherapy; LncRNA; MCL-1; MYC; Mutation; NOTCH; Non-coding RNA; Tumor suppressor; circRNA; miRNA.

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Conflict of interest statement

Authors declare no financial conflict of interest. Dr. Nicot is an editorial board member of

Figures

Fig. 1
Fig. 1
FBXW7 Regulation in the Cell. Multiple FBXW7-related expression regulators regulate FBXW7 expression in different biological processes. lncRNAs can act as sponges that bind to miRNAs and restrain the effect of miRNAs on FBXW7 expression. When the mRNA of FBXW7 is looped by the action of other loop RNAs or looped by itself, the above-mentioned FBXW7 expression regulators no longer have an effect on the expression of FBXW7
Fig. 2
Fig. 2
Methylation Profile of FBXW7. Representation of the methylation profile of FBXW7 in different cancers and how it affects disease progression (http://gdata.hrbmu.edu.cn/diseasemeth/index.html)
Fig. 3
Fig. 3
FBXW7 Genetic Mutations in Various Cancer Types. The FBXW7 gene occurs in a variety of mutation patterns including nonsense mutations, deletion mutations, and mixed mutation patterns that show different frequencies in different tumor types. Here is the distribution of different mutation patterns of FBXW7 in tissues
Fig. 4
Fig. 4
Distribution of FBXW7 Genetic Mutations in Cancer Types. Pie chart graphical distribution showing the relative percentage of different FBXW7 mutants most frequently found in human cancers
Fig. 5
Fig. 5
The Contribution of FBXW7 Genetic Mutations to Cancer Type and Progression. FBXW7 loss or mutation in prognosis and cancer progression. A The cBioportal database statistics on the incidence of FBXW7 mutations in selected tumors from relevant clinical trial information (https://www.MYCancergenome.org/). B-E Kaplan-Meier survival analysis and mutation point is performed using cBioportal on TCGA database related datasets to obtain disease-free survival curves for patients with squamous cell carcinoma of the lung, ovarian plasmacytoma, and urothelial carcinoma of the bladder (http://www.cbioportal.org/)
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References

    1. Yeh CH, Bellon M, Nicot C. FBXW7: a critical tumor suppressor of human cancers. Mol Cancer. 2018;17:115–33. - PMC - PubMed
    1. Welcker M, Orian A, Jin J, Grim JE, Harper JW, Eisenman RN, Clurman BE. The Fbw7 tumor suppressor regulates glycogen synthase kinase 3 phosphorylation-dependent c-Myc protein degradation. Proc Natl Acad Sci U S A. 2004;101:9085–9090. - PMC - PubMed
    1. Balamurugan K, Wang JM, Tsai HH, Sharan S, Anver M, Leighty R, Sterneck E. The tumour suppressor C/EBPdelta inhibits FBXW7 expression and promotes mammary tumour metastasis. EMBO J. 2010;29:4106–4117. - PMC - PubMed
    1. Pelorosso FG, Balmain A. C/EBPdelta: friend or foe? a novel role for C/EBPdelta in metastasis. EMBO J. 2010;29:4063–4065. - PMC - PubMed
    1. Min SH, Lau AW, Lee TH, Inuzuka H, Wei S, Huang P, Shaik S, Lee DY, Finn G, Balastik M, Chen CH, Luo M, Tron AE, Decaprio JA, Zhou XZ, Wei W, Lu KP. Negative regulation of the stability and tumor suppressor function of Fbw7 by the Pin1 prolyl isomerase. Mol Cell. 2012;46:771–783. - PMC - PubMed

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