Is β-Catenin a Druggable Target for Cancer Therapy?

被引：112

作者：

Cui, Can ^{[1
]}

Zhou, Xianglian ^{[1
]}

Zhang, Weidong ^{[1
,2
]}

Qu, Yi ^{[1
]}

Ke, Xisong ^{[1
]}

机构：

[1] Shanghai Univ Tradit Chinese Med, Inst Interdisciplinary Integrat Med Res, Innovat Ctr Chem Biol, Shanghai, Peoples R China

[2] Second Mil Med Univ, Sch Pharm, Shanghai, Peoples R China

来源：

TRENDS IN BIOCHEMICAL SCIENCES | 2018年 / 43卷 / 08期

关键词：

PROTEIN-PROTEIN INTERACTIONS; SMALL-MOLECULE INHIBITORS; E-CADHERIN; BETA-CATENIN-TCF4; INTERACTION; SIGNALING PATHWAYS; BREAST-CANCER; SELF-RENEWAL; MUTATIONS; GROWTH; DISCOVERY;

D O I：

10.1016/j.tibs.2018.06.003

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

Mutations of canonical Wnt signaling pathway genes frequently occur in cancer and lead to abnormal accumulation of the key effector beta-catenin. Over the past decades, a number of Wnt inhibitors have been identified through high-throughput screenings, however, very few of them target beta-catenin directly, raising questions regarding its druggability. Here, we review Wnt inhibitors with a focus on small molecules that directly bind beta-catenin, discuss the druggability of beta-catenin, and why it has rarely been targeted, especially in the cellular context. We also propose strategies to develop small molecule binding and depleting cellular beta-catenin, which are generally applicable to other difficult-to-drug or yet-to-be-drugged targets.

引用

页码：623 / 634

页数：12

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