Department of Anatomy, Faculty of Medicine and Surgery, University of Malta, MSD 2080 Msida, Malta.
Sbarro Institute for Cancer Research and Molecular Medicine, Center for Biotechnology, College of Science and Technology, Temple University, Philadelphia, PA 19122, USA.
Cells. 2023 May 17;12(10):1415. doi: 10.3390/cells12101415.
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.
F-Box 和 WD 重复结构域包含 7(FBXW7)蛋白已被证明可调节细胞生长并作为肿瘤抑制因子发挥作用。这种蛋白也称为 FBW7、hCDC4、SEL10 或 hAGO,由 FBXW7 基因编码。它是 Skp1-Cullin1-F-box(SCF)复合物的关键组成部分,SCF 复合物是一种泛素连接酶。该复合物通过泛素-蛋白酶体系统(UPS)帮助降解许多癌蛋白,如细胞周期蛋白 E、c-JUN、c-MYC、NOTCH 和 MCL1。FBXW7 基因在包括妇科癌症(GCs)在内的多种癌症中经常发生突变或缺失。由于治疗耐药性增加,这种 FBXW7 突变与预后不良有关。因此,检测 FBXW7 突变可能是一种适当的诊断和预后生物标志物,在确定合适的个体化管理方面发挥着核心作用。最近的研究还表明,在特定情况下,FBXW7 可能作为癌基因发挥作用。越来越多的证据表明,FBXW7 的异常表达参与了 GCs 的发展。本综述的目的是更新 FBXW7 作为潜在生物标志物的作用,以及作为治疗新疗法的靶点,特别是在 GCs 的管理中。