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Clathrin-Independent Endocytosis Suppresses Cancer Cell Blebbing and Invasion
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Number of Authors: 92017 (English)In: Cell reports, ISSN 2211-1247, E-ISSN 2211-1247, Vol. 20, no 8, p. 1893-1905Article in journal (Refereed) Published
Abstract [en]

Cellular blebbing, caused by local alterations in cellsurface tension, has been shown to increase the invasiveness of cancer cells. However, the regulatory mechanisms balancing cell-surface dynamics and bleb formation remain elusive. Here, we show that an acute reduction in cell volume activates clathrinindependent endocytosis. Hence, a decrease in surface tension is buffered by the internalization of the plasma membrane (PM) lipid bilayer. Membrane invagination and endocytosis are driven by the tension- mediated recruitment of the membrane sculpting and GTPase-activating protein GRAF1 (GTPase regulator associated with focal adhesion kinase-1) to the PM. Disruption of this regulation by depleting cells of GRAF1 or mutating key phosphatidylinositol- interacting amino acids in the protein results in increased cellular blebbing and promotes the 3D motility of cancer cells. Our data support a role for clathrin-independent endocytic machinery in balancing membrane tension, which clarifies the previously reported role of GRAF1 as a tumor suppressor.

Place, publisher, year, edition, pages
2017. Vol. 20, no 8, p. 1893-1905
Keywords [en]
Endocytosis, clathrin-independent endocytosis, membrane blebbing, membrane tension, GRAF1, cancer invasion, cell migration, ARHGAP26, cell surface dynamics, GRAF1-dependent endocytosis
National Category
Biological Sciences
Identifiers
URN: urn:nbn:se:su:diva-147066DOI: 10.1016/j.celrep.2017.08.006ISI: 000408154300014PubMedID: 28834752OAI: oai:DiVA.org:su-147066DiVA, id: diva2:1142414
Available from: 2017-09-19 Created: 2017-09-19 Last updated: 2017-11-29Bibliographically approved

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