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Review
. 2023 Mar 14:13:1147239.
doi: 10.3389/fonc.2023.1147239. eCollection 2023.

FBXW7 attenuates tumor drug resistance and enhances the efficacy of immunotherapy

Shimin Chen  1   2   3 , Jichun Lin  1   2   3 , Jiaojiao Zhao  1   2   3 , Qian Lin  1 , Jia Liu  4 , Qiang Wang  5 , Ryan Mui  6 , Leina Ma  1   2
Affiliations
Review

FBXW7 attenuates tumor drug resistance and enhances the efficacy of immunotherapy

Shimin Chen et al. Front Oncol. .

Abstract

FBXW7 (F-box and WD repeat domain containing 7) is a critical subunit of the Skp1-Cullin1-F-box protein (SCF), acting as an E3 ubiquitin ligase by ubiquitinating targeted protein. Through degradation of its substrates, FBXW7 plays a pivotal role in drug resistance in tumor cells and shows the potential to rescue the sensitivity of cancer cells to drug treatment. This explains why patients with higher FBXW7 levels exhibit higher survival times and more favorable prognosis. Furthermore, FBXW7 has been demonstrated to enhance the efficacy of immunotherapy by targeting the degradation of specific proteins, as compared to the inactivated form of FBXW7. Additionally, other F-box proteins have also shown the ability to conquer drug resistance in certain cancers. Overall, this review aims to explore the function of FBXW7 and its specific effects on drug resistance in cancer cells.

Keywords: E3 ligase; FBXW7; cancer; drug resistance; immunotherapy.

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Conflict of interest statement

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Figures

Figure 1
Figure 1
The figure shows the construction of FBXW7 and compares the way that FBXW7 wild type and FBXW7 mutation led to drug sensitivity and drug resistance respectively.
Figure 2
Figure 2
The situation of FBXW7 mutation is performed using cBioportal on the TCGA database (http://www.cbioportal.org/) (A) Mutation sites of FBXW7 and their mutation types. Different colors of spots indicate mutation types. Green spots represent missense mutation; black spots represent truncating mutation; brown spots represent splice mutation; purple spots represent struction variation or fusion mutation. (B) Mutation counts of FBXW7 in various cancer types. The color of these dots represent various type of mutation. This coordinate axis shows 30 types of cancers.
Figure 3
Figure 3
This figure indicates the role of FBXW7 on drug resistance in different tumors. In different tumors, the substrates of FBXW7 which take effects are not exactly the same, and the types of drugs whose sensitivity is regulated by FBXW7 also vary among different tumors.
Figure 4
Figure 4
The survival rate of patients with high and low expression is performed using Kaplan Meier plotter. (https://kmplot.com/analysis/index.php?p=service) (A) Esophageal adenocarcinoma patients who accept all anti-PD-L1 treatment shows that people with high levels of FBXW7 owns a longer survival time. (B) Urothelial carcinoma patients who accept all anti-PD-L1 treatment shows that people with high levels of FBXW7 owns a longer survival time. (C) Glioblastoma patients who accept all anti-PD-1 treatment shows that people with high levels of FBXW7 owns a longer survival time.
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Grants and funding

This work was funded by the National Natural Science Foundation of China (grant nos. 81502065, 81672926 and 81972793) and the Natural Science Foundation of Shandong Province, China (ZR2021MC039).

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