Snail-induced claudin-11 prompts collective migration for tumour progression

Ching Fei Li, Jia Yang Chen, Yang Hui Ho, Wen Hao Hsu, Liang Chun Wu, Hsin Yi Lan, Dennis Shin Shian Hsu, Shyh Kuan Tai, Ying Chih Chang, Muh Hwa Yang*

*此作品的通信作者

研究成果: Article同行評審

98 引文 斯高帕斯(Scopus)

摘要

Epithelial–mesenchymal transition (EMT) is a pivotal mechanism for cancer dissemination. However, EMT-regulated individual cancer cell invasion is difficult to detect in clinical samples. Emerging evidence implies that EMT is correlated to collective cell migration and invasion with unknown mechanisms. We show that the EMT transcription factor Snail elicits collective migration in squamous cell carcinoma by inducing the expression of a tight junctional protein, claudin-11. Mechanistically, tyrosine-phosphorylated claudin-11 activates Src, which suppresses RhoA activity at intercellular junctions through p190RhoGAP, maintaining stable cell–cell contacts. In head and neck cancer patients, the Snail–claudin-11 axis prompts the formation of circulating tumour cell clusters, which correlate with tumour progression. Overexpression of snail correlates with increased claudin-11, and both are associated with a worse outcome. This finding extends the current understanding of EMT-mediated cellular migration via a non-individual type of movement to prompt cancer progression.

原文English
頁(從 - 到)251-262
頁數12
期刊Nature Cell Biology
21
發行號2
DOIs
出版狀態Published - 1 2月 2019

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