Invited Talk

Stiff matrix induces exosome secretion to promote tumor growth

University of Pennsylvania Department of Biology, Lynch Laboratories, 433 S. University Ave. Philadelphia, PA 19104, USA

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Tissue fibrosis and extracellular matrix (ECM) stiffening promote tumor progression. The mechanisms by which ECM regulates its contacting cells have been extensively studied. However, how stiffness influences intercellular communications in the tumor microenvironment (TME) remains unknown. We found that stiff ECM stimulates the release of exosomes from cancer cells. We delineate a molecular pathway that links stiff ECM to activation of Akt, which in turn promotes Rab8 activation that drives exosome secretion. We further show that exosomes generated from cells grown on stiff ECM effectively promote tumor growth. Proteomic analysis revealed that the Notch signaling pathway is activated in cells treated with exosomes derived from tumor cells grown on stiff ECM, consistent with our gene expression analysis of liver tissues from patients. Our study reveals a molecular mechanism that regulates exosome secretion and provides insight into how mechanical properties of the ECM control the TME for tumor growth.