Epidermal Growth Factor Receptor substrate 8 (Eps8) controls Src/FAK-dependent phenotypes in squamous carcinoma cells

Christina Schoenherr; Bryan Serrels; Charlotte Proby; Debbie L. Cunningham; Jane E. Findlay; George S. Baillie; John K. Heath; Margaret C. Frame

doi:10.1242/jcs.157560

Epidermal Growth Factor Receptor substrate 8 (Eps8) controls Src/FAK-dependent phenotypes in squamous carcinoma cells

Christina Schoenherr, Bryan Serrels, Charlotte Proby, Debbie L. Cunningham, Jane E. Findlay, George S. Baillie, John K. Heath, Margaret C. Frame^*

^*Corresponding author for this work

Research output: Contribution to journal › Article › peer-review

Abstract

Eps8 is an actin regulatory scaffold protein increased in Squamous Cell Carcinoma (SCC) cells. It forms a complex with both Focal Adhesion Kinase (FAK) and c-Src in SCC cells derived from the DMBA/TPA model of skin carcinogenesis. Here, we describe two new roles for Eps8. Firstly, it controls the spatial distribution of active c-Src in a FAK-dependent manner. Specifically, Eps8 participates in, and regulates, a biochemical complex with c-Src and drives c-Src's trafficking to autophagic structures that SCC cells use to cope with high levels of active c-Src when FAK is absent. Secondly, when FAK is expressed in SCC cells, so tethering active c-Src at focal adhesion complexes, Eps8 is also recruited to focal adhesions and is required for FAK-dependent polarization and invasion. Therefore, Eps8 is a critical mediator of Src/FAK-regulated processes; it participates in specific biochemical complexes and promotes actin re-arrangements that determine c-Src's spatial localization and Src/FAK functions in invasive migration.

Original language	English
Pages (from-to)	5303-5316
Number of pages	14
Journal	Journal of Cell Science
Volume	127
Issue number	24
DOIs	https://doi.org/10.1242/jcs.157560
Publication status	Published - 15 Dec 2014

Keywords / Materials (for Non-textual outputs)

Eps8
FAK
Invasion
Autophagy
Src
Actin
FOCAL ADHESION KINASE
CANCER-CELLS
MEDIATED TRANSFORMATION
V-SRC
PROTEIN
EXPRESSION
INHIBITOR
MIGRATION
SURVIVAL
COMPLEX

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10.1242/jcs.157560

J Cell Sci-2014-Schoenherr-5303-16
© 2014. Published by The Company of Biologists Ltd This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution and reproduction in any medium provided that the original work is properly attributed.
Final published version, 4.72 MB

Invasion and metastasis; understanding and targeting an adhesion protein network - Programme Grant Renewal
Frame, M. (Principal Investigator)
UK-based charities
1/05/13 → 31/08/18
Project: Research

Cite this

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title = "Epidermal Growth Factor Receptor substrate 8 (Eps8) controls Src/FAK-dependent phenotypes in squamous carcinoma cells",

abstract = "Eps8 is an actin regulatory scaffold protein increased in Squamous Cell Carcinoma (SCC) cells. It forms a complex with both Focal Adhesion Kinase (FAK) and c-Src in SCC cells derived from the DMBA/TPA model of skin carcinogenesis. Here, we describe two new roles for Eps8. Firstly, it controls the spatial distribution of active c-Src in a FAK-dependent manner. Specifically, Eps8 participates in, and regulates, a biochemical complex with c-Src and drives c-Src's trafficking to autophagic structures that SCC cells use to cope with high levels of active c-Src when FAK is absent. Secondly, when FAK is expressed in SCC cells, so tethering active c-Src at focal adhesion complexes, Eps8 is also recruited to focal adhesions and is required for FAK-dependent polarization and invasion. Therefore, Eps8 is a critical mediator of Src/FAK-regulated processes; it participates in specific biochemical complexes and promotes actin re-arrangements that determine c-Src's spatial localization and Src/FAK functions in invasive migration.",

keywords = "Eps8, FAK, Invasion, Autophagy, Src, Actin, FOCAL ADHESION KINASE, CANCER-CELLS, MEDIATED TRANSFORMATION, V-SRC, PROTEIN, EXPRESSION, INHIBITOR, MIGRATION, SURVIVAL, COMPLEX",

author = "Christina Schoenherr and Bryan Serrels and Charlotte Proby and Cunningham, \{Debbie L.\} and Findlay, \{Jane E.\} and Baillie, \{George S.\} and Heath, \{John K.\} and Frame, \{Margaret C.\}",

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doi = "10.1242/jcs.157560",

language = "English",

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AU - Schoenherr, Christina

AU - Serrels, Bryan

AU - Proby, Charlotte

AU - Cunningham, Debbie L.

AU - Findlay, Jane E.

AU - Baillie, George S.

AU - Heath, John K.

AU - Frame, Margaret C.

PY - 2014/12/15

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N2 - Eps8 is an actin regulatory scaffold protein increased in Squamous Cell Carcinoma (SCC) cells. It forms a complex with both Focal Adhesion Kinase (FAK) and c-Src in SCC cells derived from the DMBA/TPA model of skin carcinogenesis. Here, we describe two new roles for Eps8. Firstly, it controls the spatial distribution of active c-Src in a FAK-dependent manner. Specifically, Eps8 participates in, and regulates, a biochemical complex with c-Src and drives c-Src's trafficking to autophagic structures that SCC cells use to cope with high levels of active c-Src when FAK is absent. Secondly, when FAK is expressed in SCC cells, so tethering active c-Src at focal adhesion complexes, Eps8 is also recruited to focal adhesions and is required for FAK-dependent polarization and invasion. Therefore, Eps8 is a critical mediator of Src/FAK-regulated processes; it participates in specific biochemical complexes and promotes actin re-arrangements that determine c-Src's spatial localization and Src/FAK functions in invasive migration.

AB - Eps8 is an actin regulatory scaffold protein increased in Squamous Cell Carcinoma (SCC) cells. It forms a complex with both Focal Adhesion Kinase (FAK) and c-Src in SCC cells derived from the DMBA/TPA model of skin carcinogenesis. Here, we describe two new roles for Eps8. Firstly, it controls the spatial distribution of active c-Src in a FAK-dependent manner. Specifically, Eps8 participates in, and regulates, a biochemical complex with c-Src and drives c-Src's trafficking to autophagic structures that SCC cells use to cope with high levels of active c-Src when FAK is absent. Secondly, when FAK is expressed in SCC cells, so tethering active c-Src at focal adhesion complexes, Eps8 is also recruited to focal adhesions and is required for FAK-dependent polarization and invasion. Therefore, Eps8 is a critical mediator of Src/FAK-regulated processes; it participates in specific biochemical complexes and promotes actin re-arrangements that determine c-Src's spatial localization and Src/FAK functions in invasive migration.

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KW - FOCAL ADHESION KINASE

KW - CANCER-CELLS

KW - MEDIATED TRANSFORMATION

KW - V-SRC

KW - PROTEIN

KW - EXPRESSION

KW - INHIBITOR

KW - MIGRATION

KW - SURVIVAL

KW - COMPLEX

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DO - 10.1242/jcs.157560

M3 - Article

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JO - Journal of Cell Science

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ER -

Epidermal Growth Factor Receptor substrate 8 (Eps8) controls Src/FAK-dependent phenotypes in squamous carcinoma cells

Abstract

Keywords / Materials (for Non-textual outputs)

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Projects

Invasion and metastasis; understanding and targeting an adhesion protein network - Programme Grant Renewal

Cite this