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

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The β3‐integrin endothelial adhesome regulates microtubule‐dependent cell migration. / Atkinson, Samuel J.; Gontarczyk, Aleksander M.; Alghamdi, Abdullah AA; 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.

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@article{c3b100673f874ead96ce74d95cffca09,
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 = "adhesive, endothelial, integrins, microtubules",
author = "Atkinson, {Samuel J.} and Gontarczyk, {Aleksander M.} and Alghamdi, {Abdullah AA} 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 = "6",
day = "1",
doi = "10.15252/embr.201744578",
language = "English",
volume = "19",
journal = "EMBO reports",
issn = "1469-221X",
publisher = "Nature Publishing Group",
number = "6",

}

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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 - adhesive

KW - endothelial

KW - integrins

KW - microtubules

U2 - 10.15252/embr.201744578

DO - 10.15252/embr.201744578

M3 - Article

VL - 19

JO - EMBO reports

T2 - EMBO reports

JF - EMBO reports

SN - 1469-221X

IS - 6

M1 - e44578

ER -

ID: 133450514