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

• Published in: Nature cell biology Vol. 21; no. 2; pp. 251 - 262
• Main Authors: Li, Ching-Fei, Chen, Jia-Yang, Ho, Yang-Hui, Hsu, Wen-Hao, Wu, Liang-Chun, Lan, Hsin-Yi, Hsu, Dennis Shin-Shian, Tai, Shyh-Kuan, Chang, Ying-Chih, Yang, Muh-Hwa
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 01.02.2019; Nature Publishing Group
• Subjects: 13/31; 13/51; 13/89; 13/95; 14/33; 14/63; 38/61; 59/5; 631/67; 631/80/84/2176; 631/80/84/2334; 692/699/67/1536; 82/58; Animals; Biomedical and Life Sciences; Caco-2 Cells; Cancer; Cancer cells; Cancer patients; Cancer Research; Carcinogenesis; Carcinoma; Cell adhesion & migration; Cell Biology; Cell Line, Tumor; Cell migration; Cell Movement - genetics; Cells, Cultured; Claudins - genetics; Claudins - metabolism; Correlation; Developmental Biology; Epithelial-Mesenchymal Transition - genetics; Female; Gene Expression Profiling - methods; Gene Expression Regulation, Neoplastic; Genetic aspects; Head & neck cancer; Head and neck cancer; Health aspects; HEK293 Cells; Humans; Life Sciences; Mesenchyme; Mice, Inbred BALB C; Mice, Nude; Molecular biology; Neoplasms - genetics; Neoplasms - metabolism; Neoplasms - pathology; Phenols (Class of compounds); Physiological aspects; Proteins; RhoA protein; Road construction industry; Snail Family Transcription Factors - genetics; Snail Family Transcription Factors - metabolism; Snail protein; Squamous cell carcinoma; Stem Cells; Transcription factors; Transplantation, Heterologous; Tumor Cells, Cultured; Tumors; Tyrosine
• ISSN: 1465-7392; 1476-4679; 1476-4679
• DOI: 10.1038/s41556-018-0268-z

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. Li et al. show that the epithelial–mesenchymal-transition transcription factor Snail induces claudin-11 expression and suppresses RhoA activity, thereby promoting collective migration and tumour progression in head and neck cancer.