Direct integrin alphavbeta6-ERK binding: implications for tumour growth.

Abstract:

:Blockade of the mitogen-activated protein (MAP) kinase pathway suppresses growth of colon cancer in vivo. Here we demonstrate a direct link between the extracellular signal-regulated kinase ERK2 and the growth-promoting cell adhesion molecule, integrin alphavbeta6, in colon cancer cells. Down-regulation of beta6 integrin subunit expression inhibits tumour growth in vivo and MAP kinase activity in response to serum stimulation. In alphavbeta6-expressing cells ERK2 is bound only to the beta6 subunit. The increase in cytosolic MAP kinase activity upon epidermal growth factor stimulation is all accounted for by beta6-bound ERK. Deletion of the ERK2 binding site on the beta6 cytoplasmic domain inhibits tumour growth and leads to an association between ERK and the beta5 subunit. The physical interaction between integrin alphavbeta6 and ERK2 defines a novel paradigm of integrin-mediated signalling and provides a therapeutic target for cancer treatment.

journal_name

Oncogene

journal_title

Oncogene

authors

Ahmed N,Niu J,Dorahy DJ,Gu X,Andrews S,Meldrum CJ,Scott RJ,Baker MS,Macreadie IG,Agrez MV

doi

10.1038/sj.onc.1205286

subject

Has Abstract

pub_date

2002-02-21 00:00:00

pages

1370-80

issue

9

eissn

0950-9232

issn

1476-5594

journal_volume

21

pub_type

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