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SHARPIN Inhibits Esophageal Squamous Cell Carcinoma Progression by Modulating Hippo Signaling

Authors :
Aijia Zhang
Weilong Wang
Zhijun Chen
Dan Pang
Xiaofeng Zhou
Kui Lu
Jinghan Hou
Sujie Wang
Can Gao
Benjie Lv
Ziyi Yan
Zhen Chen
Jian Zhu
Lidong Wang
Ting Zhuang
Xiumin Li
Source :
Neoplasia: An International Journal for Oncology Research, Vol 22, Iss 2, Pp 76-85 (2020)
Publication Year :
2020
Publisher :
Elsevier, 2020.

Abstract

Esophageal cancer is one of the leading malignancies worldwide, while around sixty percent of newly diagnosed cases are in China. In recent years, genome-wide sequencing studies and cancer biology studies show that Hippo signaling functions a critical role in esophageal squamous cell carcinoma (ESCC) progression, which could be a promising therapeutic targets in ESCC treatment. However, the detailed mechanisms of Hippo signaling dys-regulation in ESCC remain not clear. Here we identify SHARPIN protein as an endogenous inhibitor for YAP protein. SHARPIN depletion significantly decreases cell migration and invasion capacity in ESCC, which effects could be rescued by further YAP depletion. Depletion SHARPIN increases YAP protein level and YAP/TEAD target genes, such as CTGF and CYR61 in ESCC. Immuno-precipitation assay shows that SHARPIN associates with YAP, promoting YAP degradation possibly via inducing YAP K48-dependent poly-ubiquitination. Our study reveals a novel post-translational mechanism in modulating Hippo signaling in ESCC. Overexpression or activation of SHARPIN could be a promising strategy to target Hippo signaling for ESCC patients.

Details

Language :
English
ISSN :
14765586
Volume :
22
Issue :
2
Database :
Directory of Open Access Journals
Journal :
Neoplasia: An International Journal for Oncology Research
Publication Type :
Academic Journal
Accession number :
edsdoj.f81928bdf742415da2578fed6e95a9f7
Document Type :
article
Full Text :
https://doi.org/10.1016/j.neo.2019.12.001