1. Claudin-2 promotes colorectal cancer growth and metastasis by suppressing NDRG1 transcription.
- Author
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Mingtian Wei, Yaguang Zhang, Xuyang Yang, Pingfan Ma, Yan Li, Yangping Wu, Xiangzheng Chen, Xiangbing Deng, Tinghan Yang, Xiaobing Mao, Lei Qiu, Wenjian Meng, Bo Zhang, Ziqiang Wang, and Junhong Han
- Subjects
COLORECTAL cancer ,TUMOR growth ,METASTASIS ,CELL anatomy ,CELLULAR signal transduction - Abstract
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 promotesN-myc downstreamregulated 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 EMTrelated genes and CDKIs, suggesting CLDN2 may serve as a promising target for CRC treatment. [ABSTRACT FROM AUTHOR]
- Published
- 2021
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