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Clathrin-Independent Endocytosis Suppresses Cancer Cell Blebbing and Invasion
Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB).
Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB).
Umeå University, Faculty of Medicine, Department of Medical Biochemistry and Biophysics. Umeå University, Faculty of Medicine, Molecular Infection Medicine Sweden (MIMS).
Umeå University, Faculty of Medicine, Department of Medical Biosciences, Pathology.
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2017 (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
Cell Press , 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
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Cell and Molecular Biology
Identifiers
URN: urn:nbn:se:umu:diva-139144DOI: 10.1016/j.celrep.2017.08.006ISI: 000408154300014PubMedID: 28834752OAI: oai:DiVA.org:umu-139144DiVA, id: diva2:1141753
Available from: 2017-09-15 Created: 2017-09-15 Last updated: 2019-05-10Bibliographically approved

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Holst, Mikkel RolandVidal-Quadras, MaiteLarsson, ElinSong, JieHubert, MadlenBlomberg, JeanetteLandström, MaréneLundmark, Richard

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Holst, Mikkel RolandVidal-Quadras, MaiteLarsson, ElinSong, JieHubert, MadlenBlomberg, JeanetteLandström, MaréneLundmark, Richard
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Department of Integrative Medical Biology (IMB)Department of Medical Biochemistry and BiophysicsMolecular Infection Medicine Sweden (MIMS)Pathology
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Cell reports
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