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Mechanobiology of Disease
Friday Speaker Abstracts
37
A Mechanically Active Heterotypic Adhesion Enables Fibroblasts to Drive Cancer Cell
Invasion
Anna Labernadie
1
, Takuya Kato
2
, Agusti Brugues
1
, Xavier Serra-Picamal
1
, Stefanie Derzsi
1
,
Victor Gonzalez-Tarrago
1
, Alberto Elosegui-Artola
1
, Jordi Alcaraz
4
, Pere Roca-Cusachs
1,4
, Erik
Sahai
2
,
Xavier Trepat
1,3,5
.
1
Institute for Bioengineering of Catalonia, Barcelona, Spain,
2
The Francis Crick Institute,
London, United Kingdom,
4
University of Barcelona, Barcelona, Spain,
5
Centro de Investigación
Biomédica en Red en Bioingeniería, Biomateriales y Nanomedicina, Barcelona, Spain.
3
Institució
Catalana de Recerca i Estudis Avançats, Barcelona, Spain,
Cancer Associated Fibroblasts (CAFs) promote tumor invasion and metastasis. Here 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 β-catenin recruitment and adhesion reinforcement. Impairment of E-
cadherin/N-cadherin adhesion abrogates the ability of CAFs to guide collective cell migration in
2D and blocks cancer cell invasion in 3D. Further, N-cadherin mediates not only adhesion and
invasion but also repolarization of the CAFs away from the cancer cells. E-cadherin/N-cadherin
junctions between CAFs and cancer cells are observed in cells derived from human epidermal
carcinoma and human non-small lung cell carcinoma. Together, our findings show that a
mechanically active heterophilic adhesion between CAFs and cancer cells enables cooperative
tumor invasion.