The β3-integrin endothelial adhesome regulates microtubule-dependent cell migration

Samuel J. Atkinson; Aleksander M. Gontarczyk; Abdullah A.A. Alghamdi; Tim S. Ellison; Robert T. Johnson; Wesley J. Fowler; Benjamin M. Kirkup; Bernardo C. Silva; Bronwen E. Harry; Jochen G. Schneider; Katherine N. Weilbaecher; Mette M. Mogensen; Mark D. Bass; Maddy Parsons; Dylan R. Edwards; Stephen D. Robinson

doi:10.15252/embr.201744578

The β3-integrin endothelial adhesome regulates microtubule-dependent cell migration

Samuel J. Atkinson, Aleksander M. Gontarczyk, Abdullah A.A. Alghamdi, Tim S. Ellison, Robert T. Johnson, Wesley J. Fowler, Benjamin M. Kirkup, Bernardo C. Silva, Bronwen E. Harry, Jochen G. Schneider, Katherine N. Weilbaecher, Mette M. Mogensen, Mark D. Bass, Maddy Parsons, Dylan R. Edwards, Stephen D. Robinson

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19 Scopus citations

Abstract

Integrin β3 is seen as a key anti-angiogenic target for cancer treatment due to its expression on neovasculature, but the role it plays in the process is complex; whether it is pro- or anti-angiogenic depends on the context in which it is expressed. To understand precisely β3's role in regulating integrin adhesion complexes in endothelial cells, we characterised, by mass spectrometry, the β3-dependent adhesome. We show that depletion of β3-integrin in this cell type leads to changes in microtubule behaviour that control cell migration. β3-integrin regulates microtubule stability in endothelial cells through Rcc2/Anxa2-driven control of active Rac1 localisation. Our findings reveal that angiogenic processes, both in vitro and in vivo, are more sensitive to microtubule targeting agents when β3-integrin levels are reduced.

Original language	English
Article number	e44578
Journal	EMBO Reports
Volume	19
Issue number	7
DOIs	https://doi.org/10.15252/embr.201744578
State	Published - Jul 2018

Keywords

adhesome
endothelial
integrins
microtubules

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Atkinson, S. J., Gontarczyk, A. M., Alghamdi, A. A. A., Ellison, T. S., Johnson, R. T., Fowler, W. J., Kirkup, B. M., Silva, B. C., Harry, B. E., Schneider, J. G., Weilbaecher, K. N., Mogensen, M. M., Bass, M. D., Parsons, M., Edwards, D. R., & Robinson, S. D. (2018). The β3-integrin endothelial adhesome regulates microtubule-dependent cell migration. EMBO Reports, 19(7), Article e44578. https://doi.org/10.15252/embr.201744578

@article{ad65d1222b4b4d1a99aee4025ca81feb,

title = "The β3-integrin endothelial adhesome regulates microtubule-dependent cell migration",

abstract = "Integrin β3 is seen as a key anti-angiogenic target for cancer treatment due to its expression on neovasculature, but the role it plays in the process is complex; whether it is pro- or anti-angiogenic depends on the context in which it is expressed. To understand precisely β3's role in regulating integrin adhesion complexes in endothelial cells, we characterised, by mass spectrometry, the β3-dependent adhesome. We show that depletion of β3-integrin in this cell type leads to changes in microtubule behaviour that control cell migration. β3-integrin regulates microtubule stability in endothelial cells through Rcc2/Anxa2-driven control of active Rac1 localisation. Our findings reveal that angiogenic processes, both in vitro and in vivo, are more sensitive to microtubule targeting agents when β3-integrin levels are reduced.",

keywords = "adhesome, endothelial, integrins, microtubules",

author = "Atkinson, {Samuel J.} and Gontarczyk, {Aleksander M.} and Alghamdi, {Abdullah A.A.} and Ellison, {Tim S.} and Johnson, {Robert T.} and Fowler, {Wesley J.} and Kirkup, {Benjamin M.} and Silva, {Bernardo C.} and Harry, {Bronwen E.} and Schneider, {Jochen G.} and Weilbaecher, {Katherine N.} and Mogensen, {Mette M.} and Bass, {Mark D.} and Maddy Parsons and Edwards, {Dylan R.} and Robinson, {Stephen D.}",

note = "Publisher Copyright: {\textcopyright} 2018 The Authors. Published under the terms of the CC BY 4.0 license",

year = "2018",

month = jul,

doi = "10.15252/embr.201744578",

language = "English",

volume = "19",

journal = "EMBO Reports",

issn = "1469-221X",

number = "7",

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Atkinson, SJ, Gontarczyk, AM, Alghamdi, AAA, Ellison, TS, Johnson, RT, Fowler, WJ, Kirkup, BM, Silva, BC, Harry, BE, Schneider, JG, Weilbaecher, KN, Mogensen, MM, Bass, MD, Parsons, M, Edwards, DR & Robinson, SD 2018, 'The β3-integrin endothelial adhesome regulates microtubule-dependent cell migration', EMBO Reports, vol. 19, no. 7, e44578. https://doi.org/10.15252/embr.201744578

TY - JOUR

T1 - The β3-integrin endothelial adhesome regulates microtubule-dependent cell migration

AU - Atkinson, Samuel J.

AU - Gontarczyk, Aleksander M.

AU - Alghamdi, Abdullah A.A.

AU - Ellison, Tim S.

AU - Johnson, Robert T.

AU - Fowler, Wesley J.

AU - Kirkup, Benjamin M.

AU - Silva, Bernardo C.

AU - Harry, Bronwen E.

AU - Schneider, Jochen G.

AU - Weilbaecher, Katherine N.

AU - Mogensen, Mette M.

AU - Bass, Mark D.

AU - Parsons, Maddy

AU - Edwards, Dylan R.

AU - Robinson, Stephen D.

PY - 2018/7

Y1 - 2018/7

N2 - Integrin β3 is seen as a key anti-angiogenic target for cancer treatment due to its expression on neovasculature, but the role it plays in the process is complex; whether it is pro- or anti-angiogenic depends on the context in which it is expressed. To understand precisely β3's role in regulating integrin adhesion complexes in endothelial cells, we characterised, by mass spectrometry, the β3-dependent adhesome. We show that depletion of β3-integrin in this cell type leads to changes in microtubule behaviour that control cell migration. β3-integrin regulates microtubule stability in endothelial cells through Rcc2/Anxa2-driven control of active Rac1 localisation. Our findings reveal that angiogenic processes, both in vitro and in vivo, are more sensitive to microtubule targeting agents when β3-integrin levels are reduced.

AB - Integrin β3 is seen as a key anti-angiogenic target for cancer treatment due to its expression on neovasculature, but the role it plays in the process is complex; whether it is pro- or anti-angiogenic depends on the context in which it is expressed. To understand precisely β3's role in regulating integrin adhesion complexes in endothelial cells, we characterised, by mass spectrometry, the β3-dependent adhesome. We show that depletion of β3-integrin in this cell type leads to changes in microtubule behaviour that control cell migration. β3-integrin regulates microtubule stability in endothelial cells through Rcc2/Anxa2-driven control of active Rac1 localisation. Our findings reveal that angiogenic processes, both in vitro and in vivo, are more sensitive to microtubule targeting agents when β3-integrin levels are reduced.

KW - adhesome

KW - endothelial

KW - integrins

KW - microtubules

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DO - 10.15252/embr.201744578

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VL - 19

JO - EMBO Reports

JF - EMBO Reports

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ER -

The β3-integrin endothelial adhesome regulates microtubule-dependent cell migration

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