Clathrin-Independent Endocytosis Suppresses Cancer Cell Blebbing and Invasion
Cellular blebbing, caused by local alterations in cell-surface 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 cl...
| Main Authors: | , , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Elsevier
2017-08-01
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| Series: | Cell Reports |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S221112471731094X |
| _version_ | 1818288596977713152 |
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| author | Mikkel Roland Holst Maite Vidal-Quadras Elin Larsson Jie Song Madlen Hubert Jeanette Blomberg Magnus Lundborg Maréne Landström Richard Lundmark |
| author_facet | Mikkel Roland Holst Maite Vidal-Quadras Elin Larsson Jie Song Madlen Hubert Jeanette Blomberg Magnus Lundborg Maréne Landström Richard Lundmark |
| author_sort | Mikkel Roland Holst |
| collection | DOAJ |
| description | Cellular blebbing, caused by local alterations in cell-surface 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 clathrin-independent 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. |
| first_indexed | 2024-12-13T01:58:54Z |
| format | Article |
| id | doaj.art-2a0c27eafe414f0989737d1e9ff66866 |
| institution | Directory Open Access Journal |
| issn | 2211-1247 |
| language | English |
| last_indexed | 2024-12-13T01:58:54Z |
| publishDate | 2017-08-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Cell Reports |
| spelling | doaj.art-2a0c27eafe414f0989737d1e9ff668662022-12-22T00:03:19ZengElsevierCell Reports2211-12472017-08-012081893190510.1016/j.celrep.2017.08.006Clathrin-Independent Endocytosis Suppresses Cancer Cell Blebbing and InvasionMikkel Roland Holst0Maite Vidal-Quadras1Elin Larsson2Jie Song3Madlen Hubert4Jeanette Blomberg5Magnus Lundborg6Maréne Landström7Richard Lundmark8Integrative Medical Biology, Umeå University, 901 87 Umeå, SwedenIntegrative Medical Biology, Umeå University, 901 87 Umeå, SwedenMedical Biochemistry and Biophysics, Laboratory for Molecular Infection Medicine Sweden, Umeå University, 901 87 Umeå, SwedenMedical Biosciences, Umeå University, 901 87 Umeå, SwedenIntegrative Medical Biology, Umeå University, 901 87 Umeå, SwedenMedical Biochemistry and Biophysics, Laboratory for Molecular Infection Medicine Sweden, Umeå University, 901 87 Umeå, SwedenDepartment of Biochemistry and Biophysics, Bioinformatics Infrastructure for Life Sciences (BILS), Science for Life Laboratory, Stockholm University, 106 91 Stockholm, SwedenMedical Biosciences, Umeå University, 901 87 Umeå, SwedenIntegrative Medical Biology, Umeå University, 901 87 Umeå, SwedenCellular blebbing, caused by local alterations in cell-surface 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 clathrin-independent 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.http://www.sciencedirect.com/science/article/pii/S221112471731094XEndocytosisclathrin-independent endocytosismembrane blebbingmembrane tensionGRAF1cancer invasioncell migrationARHGAP26cell surface dynamicsGRAF1-dependent endocytosis |
| spellingShingle | Mikkel Roland Holst Maite Vidal-Quadras Elin Larsson Jie Song Madlen Hubert Jeanette Blomberg Magnus Lundborg Maréne Landström Richard Lundmark Clathrin-Independent Endocytosis Suppresses Cancer Cell Blebbing and Invasion Cell Reports Endocytosis clathrin-independent endocytosis membrane blebbing membrane tension GRAF1 cancer invasion cell migration ARHGAP26 cell surface dynamics GRAF1-dependent endocytosis |
| title | Clathrin-Independent Endocytosis Suppresses Cancer Cell Blebbing and Invasion |
| title_full | Clathrin-Independent Endocytosis Suppresses Cancer Cell Blebbing and Invasion |
| title_fullStr | Clathrin-Independent Endocytosis Suppresses Cancer Cell Blebbing and Invasion |
| title_full_unstemmed | Clathrin-Independent Endocytosis Suppresses Cancer Cell Blebbing and Invasion |
| title_short | Clathrin-Independent Endocytosis Suppresses Cancer Cell Blebbing and Invasion |
| title_sort | clathrin independent endocytosis suppresses cancer cell blebbing and invasion |
| topic | Endocytosis clathrin-independent endocytosis membrane blebbing membrane tension GRAF1 cancer invasion cell migration ARHGAP26 cell surface dynamics GRAF1-dependent endocytosis |
| url | http://www.sciencedirect.com/science/article/pii/S221112471731094X |
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