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

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

18 Citations (Scopus)

31 Downloads (Pure)

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	6
Early online date	24 May 2018
DOIs	https://doi.org/10.15252/embr.201744578
Publication status	Published - 1 Jun 2018

Keywords

adhesive
endothelial
integrins
microtubules

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

Access to Document

10.15252/embr.201744578

Accepted manuscriptAccepted author manuscript, 40.2 MB

Dylan Edwards
- Dylan.Edwardsuea.acuk
- Norwich Medical School - Emeritus Professor
- Norwich Institute for Healthy Aging - Member
- Cancer Studies - Member
Person: Honorary, Research Group Member, Research Centre Member
Mette Mogensen
- M.Mogensenuea.acuk
- School of Biological Sciences - Emeritus Reader
Person: Honorary
Stephen Robinson
- Stephen.Robinsonuea.acuk
- School of Biological Sciences - Research Leader
- Norwich Institute for Healthy Aging - Member
- Cells and Tissues - Member
Person: Research Group Member, Research Centre Member, Academic, Teaching & Research

Deciphering the angiogenic tug-of war between neuropilin-1 interacting integrins
Robinson, S. & Akbareian, S.
British Heart Foundation
21/09/15 → 20/09/16
Project: Research
Preventing anti-angiogenic escape through the endothelial adhesome
Robinson, S.
The Big C Appeal
1/03/15 → 28/02/18
Project: Research
Re-organisation of microtubule minus-ends during apico-basal epithelial polarisation and differentiation
Mogensen, M., Powell, P., Thomas, P., Wileman, T. & Goldspink, D.
Biotechnology and Biological Sciences Research Council
1/03/12 → 28/02/15
Project: Research

Cite this

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(6), [e44578]. https://doi.org/10.15252/embr.201744578

Atkinson, Samuel J. ; Gontarczyk, Aleksander M. ; Alghamdi, Abdullah A. A. ; Ellison, Tim S. ; Johnson, Robert T. ; Fowler, Wesley J. ; Kirkup, Benjamin M. ; Silva, Bernardo C. ; Harry, Bronwen E. ; Schneider, Jochen G. ; Weilbaecher, Katherine N. ; Mogensen, Mette M. ; Bass, Mark D. ; Parsons, Maddy ; Edwards, Dylan R. ; Robinson, Stephen D. / The β3‐integrin endothelial adhesome regulates microtubule‐dependent cell migration. In: EMBO Reports. 2018 ; Vol. 19, No. 6.

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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{\textquoteright}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 = "adhesive, 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.}",

year = "2018",

month = jun,

day = "1",

doi = "10.15252/embr.201744578",

language = "English",

volume = "19",

journal = "EMBO Reports",

issn = "1469-221X",

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number = "6",

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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. 6, e44578. https://doi.org/10.15252/embr.201744578

The β3‐integrin endothelial adhesome regulates microtubule‐dependent cell migration. / Atkinson, Samuel J.; Gontarczyk, Aleksander M.; Alghamdi, Abdullah A. A.; Ellison, Tim S.; Johnson, Robert T.; Fowler, Wesley J.; Kirkup, Benjamin M.; Silva, Bernardo C.; Harry, Bronwen E.; Schneider, Jochen G.; Weilbaecher, Katherine N.; Mogensen, Mette M.; Bass, Mark D.; Parsons, Maddy ; Edwards, Dylan R.; Robinson, Stephen D.

In: EMBO Reports, Vol. 19, No. 6, e44578, 01.06.2018.

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

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 - 2018/6/1

Y1 - 2018/6/1

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 - adhesive

KW - endothelial

KW - integrins

KW - microtubules

U2 - 10.15252/embr.201744578

DO - 10.15252/embr.201744578

M3 - Article

VL - 19

JO - EMBO Reports

JF - EMBO Reports

SN - 1469-221X

IS - 6

M1 - e44578

ER -

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

Abstract

Keywords

UN SDGs

Access to Document

Profiles

Dylan Edwards

Mette Mogensen

Stephen Robinson

Projects

Deciphering the angiogenic tug-of war between neuropilin-1 interacting integrins

Preventing anti-angiogenic escape through the endothelial adhesome

Re-organisation of microtubule minus-ends during apico-basal epithelial polarisation and differentiation

Cite this