RACO-1 modulates Hippo signalling in oesophageal squamous cell carcinoma

Dan Pang; Weilong Wang; Xiaofeng Zhou; Kui Lu; Jinghang Zhang; Zhiguo Chen; Lingchao Wang; Fangfang Shen; Zhen Chen; Sujie Wang; Jinghan Hou; Aijia Zhang; Benjie Lv; Can Gao; Ziyi Yan; Yuhan Hu; Tingmin Chang; Lidong Wang; Xiumin Li

doi:10.1111/jcmm.15811

RACO-1 modulates Hippo signalling in oesophageal squamous cell carcinoma

J Cell Mol Med. 2020 Oct;24(20):11912-11921. doi: 10.1111/jcmm.15811. Epub 2020 Sep 7.

Authors

Dan Pang^{1

2}, Weilong Wang^{1

2}, Xiaofeng Zhou², Kui Lu^{1

2}, Jinghang Zhang³, Zhiguo Chen⁴, Lingchao Wang⁵, Fangfang Shen⁶, Zhen Chen², Sujie Wang², Jinghan Hou^{1

2}, Aijia Zhang^{1

2}, Benjie Lv^{1

2}, Can Gao^{1

2}, Ziyi Yan², Yuhan Hu⁷, Tingmin Chang⁸, Lidong Wang⁹, Xiumin Li^{1

2}

Affiliations

¹ Department of Gastroenterology, The Third Affiliated Hospital of Xinxiang Medical University, Xinxiang, China.
² Xinxiang Key Laboratory for Molecular Therapy of Cancer, Xinxiang Medical University, Xinxiang, China.
³ Department of Pathology, The First Affiliated Hospital of Xinxiang Medical University, Xinxiang, China.
⁴ Department of Human Anatomy, Department of Basic Medical Sciences, Xinxiang Medical University, Xinxiang, China.
⁵ Department of Pediatrics, the First Affiliated Hospital of Xinxiang Medical University, Xinxiang, China.
⁶ Xinxiang Key Lab of Translational Cancer Research, The Third Affiliated Hospital of Xinxiang Medical University, Xinxiang, China.
⁷ Department of Pathology, School of Basic Medical Sciences, Xinxiang Medical University, Xinxiang, China.
⁸ Department of Gastroenterology, The First Affiliated Hospital of Xinxiang Medical University, Xinxiang, China.
⁹ State Key Laboratory of Esophageal Cancer Prevention & Treatment and Henan Key Laboratory for Esophageal Cancer Research, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China.

Abstract

Oesophageal cancer is one of the most lethal malignancies worldwide, whereas the 5-year survival is less than 20%. Although the detailed carcinogenic mechanisms are not totally clear, recent genomic sequencing data showed dysregulation of Hippo signalling could be a critical factor for oesophageal squamous cell carcinoma (ESCC) progression. Therefore, understanding of the molecular mechanisms that control Hippo signalling activity is of great importance to improve ESCC diagnostics and therapeutics. Our current study revealed RACO-1 as an inhibitory protein for YAP/TEAD axis. Depletion of RACO-1 increases the protein level of YAP and expression of YAP/TEAD target gene. Besides, RACO-1 silencing could promote ESCC cell invasion and migration, which effect could be rescued by YAP depletion in ESCC cells. Immunoprecipitation showed that RACO-1 associated with YAP and promote ubiquitination and degradation of YAP at k48 poly-ubiquitination site. Our research discovered a new regulator of Hippo signalling via modulating YAP stability. RACO-1 could be a promising factor, which serves cancer diagnostics and therapeutics in ESCC patients.

Keywords: Hippo; Oesophageal squamous cell carcinoma; RACO-1; Ubiquitin; YAP.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Cell Line, Tumor
Cell Movement
Esophageal Neoplasms / metabolism*
Esophageal Squamous Cell Carcinoma / metabolism*
Hippo Signaling Pathway
Humans
Models, Biological
Neoplasm Invasiveness
Protein Serine-Threonine Kinases / metabolism*
Protein Stability
Proteolysis
Signal Transduction*
Trans-Activators / metabolism*
Ubiquitin-Protein Ligases / metabolism*
Ubiquitination

Substances

Trans-Activators
RNF187 protein, human
Ubiquitin-Protein Ligases
Protein Serine-Threonine Kinases