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

被引：119

作者：

Li, Ching-Fei ^{[1
,2
,3
]}

Chen, Jia-Yang ^{[4
]}

Ho, Yang-Hui ^{[4
]}

Hsu, Wen-Hao ^{[3
]}

Wu, Liang-Chun ^{[4
]}

Lan, Hsin-Yi ^{[3
]}

Hsu, Dennis Shin-Shian ^{[5
]}

Tai, Shyh-Kuan ^{[6
]}

Chang, Ying-Chih ^{[4
]}

Yang, Muh-Hwa ^{[1
,2
,3
,5
,7
]}

机构：

[1] Natl Yang Ming Univ, Program Mol Med, Taipei, Taiwan

[2] Acad Sinica, Taipei, Taiwan

[3] Natl Yang Ming Univ, Inst Clin Med, Taipei, Taiwan

[4] Acad Sinica, Genom Res Ctr, Taipei, Taiwan

[5] Natl Yang Ming Univ, Canc Progress Res Ctr, Taipei, Taiwan

[6] Taipei Vet Gen Hosp, Dept Otolaryngol, Taipei, Taiwan

[7] Taipei Vet Gen Hosp, Div Med Oncol, Dept Oncol, Taipei, Taiwan

来源：

NATURE CELL BIOLOGY | 2019年 / 21卷 / 02期

关键词：

FOCAL-ADHESION KINASE; CELL-CELL CONTACTS; CARCINOMA-CELLS; TIGHT JUNCTIONS; CANCER-CELLS; INVASION; GROWTH; PHOSPHORYLATION; EXPRESSION; HEAD;

D O I：

10.1038/s41556-018-0268-z

中图分类号：

Q2 [细胞生物学];

学科分类号：

071009 ; 090102 ;

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.

引用

页码：251 / +

页数：14

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