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FBXW7 在乳腺癌中的作用机制和治疗潜力。

FBXW7 in breast cancer: mechanism of action and therapeutic potential.

机构信息

Chongqing Key Laboratory of Sichuan-Chongqing Co-Construction for Diagnosisand, Treatment of Infectious Diseases Integrated Traditional Chinese and Western Medicine, College of Medical Technology , Chengdu University of Traditional Chinese Medicine, Chengdu, China.

出版信息

J Exp Clin Cancer Res. 2023 Sep 2;42(1):226. doi: 10.1186/s13046-023-02767-1.

Abstract

Breast cancer is one of the frequent tumors that seriously endanger the physical and mental well-being in women. F-box and WD repeat domain-containing 7 (FBXW7) is a neoplastic repressor. Serving as a substrate recognition element for ubiquitin ligase, FBXW7 participates in the ubiquitin-proteasome system and is typically in charge of the ubiquitination and destruction of crucial oncogenic proteins, further performing a paramount role in cell differentiation, apoptosis and metabolic processes. Low levels of FBXW7 cause abnormal stability of pertinent substrates, mutations and/or deletions in the FBXW7 gene have been reported to correlate with breast cancer malignant progression and chemoresistance. Given the lack of an effective solution to breast cancer's clinical drug resistance dilemma, elucidating FBXW7's mechanism of action could provide a theoretical basis for targeted drug exploration. Therefore, in this review, we focused on FBXW7's role in a range of breast cancer malignant behaviors and summarized the pertinent cellular targets, signaling pathways, as well as the mechanisms regulating FBXW7 expression. We also proposed novel perspectives for the exploitation of alternative therapies and specific tumor markers for breast cancer by therapeutic strategies aiming at FBXW7.

摘要

乳腺癌是严重危害女性身心健康的常见肿瘤之一。F-box 和 WD 重复域蛋白 7(FBXW7)是一种肿瘤抑制因子。作为泛素连接酶的底物识别元件,FBXW7 参与泛素-蛋白酶体系统,通常负责关键致癌蛋白的泛素化和降解,在细胞分化、凋亡和代谢过程中发挥着重要作用。FBXW7 水平降低会导致相关底物的稳定性异常,FBXW7 基因的突变和/或缺失与乳腺癌的恶性进展和化疗耐药性相关。鉴于缺乏解决乳腺癌临床耐药性难题的有效方法,阐明 FBXW7 的作用机制可为靶向药物探索提供理论依据。因此,在本综述中,我们重点关注了 FBXW7 在多种乳腺癌恶性行为中的作用,并总结了相关的细胞靶标、信号通路以及调节 FBXW7 表达的机制。我们还提出了通过针对 FBXW7 的治疗策略来开发乳腺癌替代治疗方法和特定肿瘤标志物的新视角。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fe51/10474666/35b1e4535657/13046_2023_2767_Fig1_HTML.jpg

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