Direct integrin αvβ6-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 αvβ6, in colon cancer cells. Down-regulation of β6 integrin subunit expression inhibits tumour growth in vivo and MAP kinase activity in response to serum stimulation. In αvβ6-expressing cells ERK2 is bound only to the β6 subunit. The increase in cytosolic MAP kinase activity upon epidermal growth factor stimulation is all accounted for by β6-bound ERK. Deletion of the ERK2 binding site on the β6 cytoplasmic domain inhibits tumour growth and l..