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
Oncogenejournal_title
Oncogeneauthors
Ahmed N,Niu J,Dorahy DJ,Gu X,Andrews S,Meldrum CJ,Scott RJ,Baker MS,Macreadie IG,Agrez MVdoi
10.1038/sj.onc.1205286subject
Has Abstractpub_date
2002-02-21 00:00:00pages
1370-80issue
9eissn
0950-9232issn
1476-5594journal_volume
21pub_type
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