Claudin-2 promotes colorectal cancer growth and metastasis by suppressing NDRG1 transcription

被引：43

作者：

Wei, Mingtian ^{[1
,2
]}

Zhang, Yaguang ^{[3
]}

Yang, Xuyang ^{[1
,2
]}

Ma, Pingfan ^{[3
]}

Li, Yan ^{[3
]}

Wu, Yangping ^{[4
,5
]}

Chen, Xiangzheng ^{[6
]}

Deng, Xiangbing ^{[1
,2
]}

Yang, Tinghan ^{[1
,2
]}

Mao, Xiaobing ^{[3
]}

Qiu, Lei ^{[3
]}

Meng, Wenjian ^{[1
,2
]}

Zhang, Bo ^{[1
,2
,3
]}

Wang, Ziqiang ^{[1
,2
]}

Han, Junhong ^{[3
]}

机构：

[1] Sichuan Univ, Dept Gastrointestinal Surg, Frontiers Sci Ctr Dis Related Mol Network, West China Hosp, Chengdu, Peoples R China

[2] Sichuan Univ, State Key Lab Biotherapy, West China Hosp, Chengdu, Peoples R China

[3] Sichuan Univ, Res Lab Tumors Epigenet & Genom, Dept Gen Surg,West China Hosp, Frontiers Sci Ctr Dis Related Mol Network,State K, 17 Peoples South Rd Third Sect, Chengdu 610041, Peoples R China

[4] Sichuan Univ, West China Hosp, Dept Resp & Crit Care Med, State Key Lab Biotherapy, Chengdu, Peoples R China

[5] Sichuan Univ, West China Hosp, Dept Clin Res Management, Chengdu, Peoples R China

[6] Sichuan Univ, West China Hosp, Dept Liver Surg & Liver Transplantat Ctr, Chengdu, Peoples R China

来源：

CLINICAL AND TRANSLATIONAL MEDICINE | 2021年 / 11卷 / 12期

基金：

中国博士后科学基金; 中国国家自然科学基金;

关键词：

CLDN2; colorectal cancer; NDRG1; progression; ZONAB; FACTOR RECEPTOR; EMT; EXPRESSION; TUMORIGENICITY; PROLIFERATION; INITIATION; MECHANISM; PATHWAYS; ROLES; CELLS;

D O I：

10.1002/ctm2.667

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

Colorectal cancer (CRC) is one of the most common malignant tumours, with multiple driving factors and biological transitions involved in its development. Claudin-2 (CLDN2), a well-defined component of cellular tight junction, has been indicated to associate with CRC progression. However, the function of CLDN2 and the underlying mechanism whereby the downstream signalling transduction is regulated in CRC remains largely unclear. In this study, we demonstrated that CLDN2 is upregulated in CRC samples and associated with poor survival. And CLDN2 depletion significantly promotes N-myc downstream-regulated gene 1 (NDRG1) transcription, leading to termination of the CRC growth and metastasis in vitro and in vivo. Mechanistically, this process promotes CLDN2/ZO1/ZONAB complex dissociation and ZONAB shuttle into nucleus to enrich in the promoter of NDRG1. Thus, this study reveals a novel CLDN2/ZO1/ZONAB-NDRG1 axis in CRC by regulating the expression of EMT-related genes and CDKIs, suggesting CLDN2 may serve as a promising target for CRC treatment.

引用

页数：17

共 48 条

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