Editors' ChoiceCancer

Linking integrins and EVs in metastasis

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Science Signaling  15 Sep 2020:
Vol. 13, Issue 649, eabe3353
DOI: 10.1126/scisignal.abe3353

Integrins mediate the uptake of extracellular vesicles into breast cancer cells.

Small extracellular vesicles (EVs) carry protein, RNA, and other cargo between cells. Integrins mediate both cell adhesion to the extracellular matrix and, in some cases, the entry of viruses into cells. In addition to their roles in normal development and physiology, both EVs and integrins are implicated in pathophysiology, notably stress resistance and metastatic progression in tumors. Fuentes et al. uncovered a direct link between these, finding that integrin β3 mediates the uptake of EVs into triple-negative breast cancer (TNBC) cells. Integrin β3 was critical for EV uptake and EV-induced colony growth in MDA-MB-231 cells. EV uptake was codependent on the transient binding of EVs to a group of cell surface glycoproteins called HSPGs and subsequently rapid endocytosis mediated by integrin-induced activation of the kinase FAK. Curiously, integrin β3 also modulated the cell’s own EV production and contents. Knocking down integrin β3 induced a shift in the size of EV produced, increasing the number of smaller EVs while decreasing the number of larger ones. Uptake and colony formation in recipient cells were unaffected, but the altered protein content of EVs from integrin β3–knockdown cells did not induce migration, in contrast to those from control cells. These findings reveal how integrins mediate intercellular signaling by EVs and indicate that integrin expression may influence the functional diversity of EVs.

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