A mechanically active heterotypic E-cadherin/N-cadherin adhesion enables fibroblasts to drive cancer cell invasion

被引：603

作者：

Labernadie, Anna ^{[1
]}

Kato, Takuya ^{[2
]}

Brugues, Agusti ^{[1
]}

Serra-Picamal, Xavier ^{[1
,3
]}

Derzsi, Stefanie ^{[2
]}

Arwert, Esther ^{[2
]}

Weston, Anne ^{[2
]}

Gonzalez-Tarrago, Victor ^{[1
]}

Elosegui-Artola, Alberto ^{[1
]}

Albertazzi, Lorenzo ^{[1
]}

Alcaraz, Jordi ^{[3
]}

Roca-Cusachs, Pere ^{[1
,3
]}

Sahai, Erik ^{[2
]}

Trepat, Xavier ^{[1
,3
,4
,5
]}

机构：

[1] Inst Bioengn Catalonia, Barcelona 08028, Spain

[2] Francis Crick Inst, 1 Midland Rd, London NW1 1AT, England

[3] Univ Barcelona, Fac Med, Unitat Biofis & Bioengn, E-08036 Barcelona, Spain

[4] ICREA, Barcelona 08010, Spain

[5] Ctr Invest Biomed Red Bioingn Biomat & Nanomed, Barcelona 08028, Spain

来源：

NATURE CELL BIOLOGY | 2017年 / 19卷 / 03期

基金：

欧洲研究理事会; 英国惠康基金; 英国医学研究理事会;

关键词：

REGULATES CONTACT INHIBITION; BREAST-CANCER; MESENCHYMAL TRANSITION; TUMOR MICROENVIRONMENT; COLLECTIVE INVASION; ADHERENS JUNCTIONS; ALPHA-CATENIN; MIGRATION; FORCES; LOCOMOTION;

D O I：

10.1038/ncb3478

中图分类号：

Q2 [细胞生物学];

学科分类号：

071009 ; 090102 ;

摘要：

Cancer-associated fibroblasts (CAFs) promote tumour invasion and metastasis. We show that CAFs exert a physical force on cancer cells that enables their collective invasion. Force transmission is mediated by a heterophilic adhesion involving N-cadherin at the CAF membrane and E-cadherin at the cancer cell. membrane. This adhesion is mechanically active; when subjected to force it triggers beta-catenin recruitment and adhesion reinforcement dependent on alpha-catenin/vinculin interaction. Impairment of E-cadherin/N-cadherin adhesion abrogates the ability of CAFs to guide collective cell migration and blocks cancer cell invasion. N-cadherin also mediates repolarization of the CAFs away from the cancer cells. In parallel, nectins and afadin are recruited to the cancer cell/CAF interface and CAF repolarization is afadin dependent. Heterotypic junctions between CAFs and cancer cells are observed in patient-derived material. Together, our findings show that a mechanically active heterophilic adhesion between CAFs and cancer cells enables cooperative tumour invasion.

引用

页码：224 / 237

页数：14

共 60 条

[1] CONTACT INHIBITION AND MALIGNANCY [J].