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

Ekrem Emrah Er, Manuel Valiente, Karuna Ganesh, Yilong Zou, Saloni Agrawal, Jing Hu, Bailey Griscom, Marc Rosenblum, Adrienne Boire, Edi Brogi, Filippo G. Giancotti, Melitta Schachner, Srinivas Malladi, Joan Massagué

Research output: Contribution to journalArticle

38 Scopus citations

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.

Original languageEnglish (US)
JournalNature Cell Biology
DOIs
StateAccepted/In press - Jan 1 2018

ASJC Scopus subject areas

  • Cell Biology

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    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. (Accepted/In press). Pericyte-like spreading by disseminated cancer cells activates YAP and MRTF for metastatic colonization. Nature Cell Biology. https://doi.org/10.1038/s41556-018-0138-8