Pericyte-like spreading by disseminated cancer cells activates YAP and MRTF for metastatic colonization Journal Article


Authors: Er, E. E.; Valiente, M.; Ganesh, K.; Zou, Y.; Agrawal, S.; Hu, J.; Griscom, B.; Rosenblum, M.; Boire, A.; Brogi, E.; Giancotti, F. G.; Schachner, M.; Malladi, S.; Massagué, J.
Article Title: Pericyte-like spreading by disseminated cancer cells activates YAP and MRTF for metastatic colonization
Abstract: Metastatic seeding by disseminated cancer cells principally occurs in perivascular niches. Here, we show that mechanotransduction signalling triggered by the pericyte-like spreading of disseminated cancer cells on host tissue capillaries is critical for metastatic colonization. Disseminated cancer cells employ L1CAM (cell adhesion molecule L1) to spread on capillaries and activate the mechanotransduction effectors YAP (Yes-associated protein) and MRTF (myocardin-related transcription factor). This spreading is robust enough to displace resident pericytes, which also use L1CAM for perivascular spreading. L1CAM activates YAP by engaging β1 integrin and ILK (integrin-linked kinase). L1CAM and YAP signalling enables the outgrowth of metastasis-initiating cells both immediately following their infiltration of target organs and after they exit from a period of latency. Our results identify an important step in the initiation of metastatic colonization, define its molecular constituents and provide an explanation for the widespread association of L1CAM with metastatic relapse in the clinic. © 2018, The Author(s).
Journal Title: Nature Cell Biology
Volume: 20
Issue: 8
ISSN: 1465-7392
Publisher: Nature Publishing Group  
Date Published: 2018-08-01
Start Page: 966
End Page: 978
Language: English
DOI: 10.1038/s41556-018-0138-8
PROVIDER: scopus
PUBMED: 30038252
DOI/URL:
Notes: Article -- Export Date: 4 September 2018 -- Source: Scopus
Altmetric Score
MSK Authors
  1. Marc Rosenblum
    249 Rosenblum
  2. Joan Massague
    276 Massague
  3. Edi Brogi
    304 Brogi
  4. Adrienne Boire
    19 Boire
  5. Yilong Zou
    13 Zou
  6. Karuna   Ganesh
    8 Ganesh
  7. Ekrem Emrah   Er
    2 Er
  8. Jing   Hu
    2 Hu