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

TY - JOUR

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

AU - Atkinson, Samuel J.

AU - Gontarczyk, Aleksander M.

AU - Alghamdi, Abdullah Aa

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 - Adhesome

KW - Endothelial

KW - Integrins

KW - Microtubules

UR - https://www.scopus.com/pages/publications/85047524602

U2 - 10.15252/embr.201744578

DO - 10.15252/embr.201744578

M3 - Article

AN - SCOPUS:85047524602

SN - 1469-221X

JO - EMBO Reports

JF - EMBO Reports

ER -