4.7 Review

Clinical significance of FBXW7 loss of function in human cancers

期刊

MOLECULAR CANCER
卷 21, 期 1, 页码 -

出版社

BMC
DOI: 10.1186/s12943-022-01548-2

关键词

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

资金

  1. [R01CA201309]

向作者/读者索取更多资源

FBXW7 is a component of the SCF/beta-TrCP complex and plays a role in phosphorylation-dependent ubiquitination and proteasome degradation of oncoproteins. It affects various regulatory functions and its dysregulation is associated with cancer. FBXW7 expression and functions are regulated through multiple mechanisms, and its inactivation is frequently observed in lung, colon, and hematopoietic cancers. Mutations in FBXW7 result in differential degradation of specific cellular targets, leading to distinct activation/inactivation patterns in cell signaling pathways.
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/beta-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.

作者

我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。

评论

主要评分

4.7
评分不足

次要评分

新颖性
-
重要性
-
科学严谨性
-
评价这篇论文

推荐

暂无数据
暂无数据