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oai:repisalud.isciii.es:20.500.12105/258722025-12-18T12:56:22Zcom_20.500.12105_2327com_20.500.12105_2290col_20.500.12105_16991

00925njm 22002777a 4500 dc Er, Ekrem Emrah author Valiente, Manuel author Ganesh, Karuna author Zou, Yilong author Agrawal, Saloni author Hu, Jing author Griscom, Bailey author Rosenblum, Marc author Boire, Adrienne author Brogi, Edi author Giancotti, Filippo G author Schachner, Melitta author Malladi, Srinivas author Massagué, Joan author 2018-08 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 β 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. Nat Cell Biol . 2018 Aug;20(8):966-978. https://hdl.handle.net/20.500.12105/25872 30038252 Nature Cell Biology https://pmc.ncbi.nlm.nih.gov/articles/PMC6467203/pdf/nihms-1012288.pdf TRANSLATIONAL PROFILING APPROACH ADHESION MOLECULE CO-OPTION GROWTH PATHWAY L1CAM TRANSCRIPTION EXPRESSION INDUCTION DYNAMICS Pericyte-like spreading by disseminated cancer cells activates YAP and MRTF for metastatic colonization.