RACK1 facilitates breast cancer progression by competitively inhibiting the binding of β-catenin to PSMD2 and enhancing the stability of β-catenin

Author:

Tian RuinanORCID,Tian Jianfei,Zuo Xiaoyan,Ren Sixin,Zhang He,Liu Hui,Wang Zhiyong,Cui Yanfen,Niu RuifangORCID,Zhang FeiORCID

Abstract

AbstractThe receptor for activated C kinase 1 (RACK1) is a key scaffolding protein with multifunctional and multifaceted properties. By mediating protein-protein interactions, RACK1 integrates multiple intracellular signals involved in the regulation of various physiological and pathological processes. Dysregulation of RACK1 has been implicated in the initiation and progression of many tumors. However, the exact function of RACK1 in cancer cellular processes, especially in proliferation, remains controversial. Here, we show that RACK1 is required for breast cancer cell proliferation in vitro and tumor growth in vivo. This effect of RACK1 is associated with its ability to enhance β-catenin stability and activate the canonical WNT signaling pathway in breast cancer cells. We identified PSMD2, a key component of the proteasome, as a novel binding partner for RACK1 and β-catenin. Interestingly, although there is no interaction between RACK1 and β-catenin, RACK1 binds PSMD2 competitively with β-catenin. Moreover, RACK1 prevents ubiquitinated β-catenin from binding to PSMD2, thereby protecting β-catenin from proteasomal degradation. Collectively, our findings uncover a novel mechanism by which RACK1 increases β-catenin stability and promotes breast cancer proliferation.

Funder

National Natural Science Foundation of China

Tianjin Medical University

Natural Science Foundation of Tianjin Municipal Science and Technology Commission

Changjiang Scholar Program of Chinese Ministry of Education

Publisher

Springer Science and Business Media LLC

Subject

Cancer Research,Cell Biology,Cellular and Molecular Neuroscience,Immunology

同舟云学术

1.学者识别学者识别

2.学术分析学术分析

3.人才评估人才评估

"同舟云学术"是以全球学者为主线,采集、加工和组织学术论文而形成的新型学术文献查询和分析系统,可以对全球学者进行文献检索和人才价值评估。用户可以通过关注某些学科领域的顶尖人物而持续追踪该领域的学科进展和研究前沿。经过近期的数据扩容,当前同舟云学术共收录了国内外主流学术期刊6万余种,收集的期刊论文及会议论文总量共计约1.5亿篇,并以每天添加12000余篇中外论文的速度递增。我们也可以为用户提供个性化、定制化的学者数据。欢迎来电咨询!咨询电话:010-8811{复制后删除}0370

www.globalauthorid.com

TOP

Copyright © 2019-2024 北京同舟云网络信息技术有限公司
京公网安备11010802033243号  京ICP备18003416号-3