Publications
>
Article

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

Publicated to:Nature Cell Biology. 19 (3): 224-237 - 2017-03-01 19(3), DOI: 10.1038/ncb3478

Authors: Labernadie, A; Kato, T; Brugués, A; Serra-Picamal, X; Derzsi, S; Arwert, E; Weston, A; González-Tarragó, V; Elosegui-Artola, A; Albertazzi, L; Alcaraz, J; Roca-Cusachs, P; Sahai, E; Trepat, X

Affiliations

Cellular and Molecular Mechanobiology. Institute for Bioengineering of Catalonia - Author
CIBER Bioingenieria, Biomateriales y Nanomedicina - Author
Ctr Invest Biomed Red Bioingn Biomat & Nanomed, Barcelona 08028, Spain - Author
Francis Crick Inst, 1 Midland Rd, London NW1 1AT, England - Author
ICREA, Barcelona 08010, Spain - Author
Inst Bioengn Catalonia, Barcelona 08028, Spain - Author
Institució Catalana de Recerca i Estudis Avançats - Author
Institute for Bioengineering of Catalonia - Author
Instituto de Bioingeniería de Cataluña - Author
Integrative Cell and Tissue Dynamics. Institute for Bioengineering of Catalonia - Author
Nanoscopy for Nanomedicine. Institute for Bioengineering of Catalonia - Author
The Francis Crick Institute - Author
Univ Barcelona, Fac Med, Unitat Biofis & Bioengn, E-08036 Barcelona, Spain - Author
Universitat de Barcelona - Author
See more

Abstract

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 β-catenin recruitment and adhesion reinforcement dependent on α-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.

Keywords
Adherens junctionsAlpha-cateninBreast-cancerCollective invasionForcesLocomotionMesenchymal transitionMigrationRegulates contact inhibitionTumor microenvironment

Quality index

Bibliometric impact. Analysis of the contribution and dissemination channel

The work has been published in the journal Nature Cell Biology due to its progression and the good impact it has achieved in recent years, according to the agency WoS (JCR), it has become a reference in its field. In the year of publication of the work, 2017, it was in position 7/190, thus managing to position itself as a Q1 (Primer Cuartil), in the category Cell Biology. Notably, the journal is positioned above the 90th percentile.

This publication has been distinguished as a “Highly Cited Paper” by the agencies WoS (ESI, Clarivate) and ESI (Clarivate), meaning that it ranks within the top 1% of the most cited articles in its thematic field during the year of its publication. In terms of the observed impact of the contribution, this work is considered one of the most influential worldwide, as it is recognized as highly cited. (source consulted: ESI Nov 14, 2024)

And this is evidenced by the extremely high normalized impacts through some of the main indicators of this type, which, although dynamic over time and dependent on the set of average global citations at the time of calculation, already indicate that they are well above the average in different agencies:

  • Normalization of citations relative to the expected citation rate (ESI) by the Clarivate agency: 12.43 (source consulted: ESI Nov 14, 2024)
  • Weighted Average of Normalized Impact by the Scopus agency: 14.31 (source consulted: FECYT Feb 2024)
  • Field Citation Ratio (FCR) from Dimensions: 61.52 (source consulted: Dimensions May 2025)

Specifically, and according to different indexing agencies, this work has accumulated citations as of 2025-05-21, the following number of citations:

  • WoS: 552
  • Scopus: 594
  • Europe PMC: 360
  • Google Scholar: 652
  • OpenCitations: 589
Impact and social visibility

From the perspective of influence or social adoption, and based on metrics associated with mentions and interactions provided by agencies specializing in calculating the so-called "Alternative or Social Metrics," we can highlight as of 2025-05-21:

  • The use, from an academic perspective evidenced by the Altmetric agency indicator referring to aggregations made by the personal bibliographic manager Mendeley, gives us a total of: 982.
  • The use of this contribution in bookmarks, code forks, additions to favorite lists for recurrent reading, as well as general views, indicates that someone is using the publication as a basis for their current work. This may be a notable indicator of future more formal and academic citations. This claim is supported by the result of the "Capture" indicator, which yields a total of: 984 (PlumX).

With a more dissemination-oriented intent and targeting more general audiences, we can observe other more global scores such as:

  • The Total Score from Altmetric: 154.834.
  • The number of mentions on the social network Facebook: 1 (Altmetric).
  • The number of mentions on the social network X (formerly Twitter): 193 (Altmetric).

It is essential to present evidence supporting full alignment with institutional principles and guidelines on Open Science and the Conservation and Dissemination of Intellectual Heritage. A clear example of this is:

  • The work has been submitted to a journal whose editorial policy allows open Open Access publication.
Leadership analysis of institutional authors

This work has been carried out with international collaboration, specifically with researchers from: United Kingdom.

There is a significant leadership presence as some of the institution’s authors appear as the first or last signer, detailed as follows: First Author (Labernadie, Anna) and Last Author (Trepat, Xavier).

the author responsible for correspondence tasks has been Trepat, Xavier.