Ahmed Nuzhat, Niu Jun, Dorahy Douglas J, Gu Xinhua, Andrews Sarah, Meldrum Cliff J, Scott Rodney J, Baker Mark S, Macreadie Ian G, Agrez Michael V
Gynaecological Cancer Research Centre, The Royal Women's Hospital, Melbourne and University of Melbourne, Melbourne, Australia.
Oncogene. 2002 Feb 21;21(9):1370-80. doi: 10.1038/sj.onc.1205286.
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.
丝裂原活化蛋白（MAP）激酶途径的阻断可抑制体内结肠癌的生长。在此，我们证明了结肠癌细胞中细胞外信号调节激酶ERK2与促进生长的细胞粘附分子整合素αvβ6之间存在直接联系。β6整合素亚基表达的下调可抑制体内肿瘤生长以及血清刺激后的MAP激酶活性。在表达αvβ6的细胞中，ERK2仅与β6亚基结合。表皮生长因子刺激后胞质MAP激酶活性的增加完全是由与β6结合的ERK引起的。β6胞质结构域上ERK2结合位点的缺失可抑制肿瘤生长，并导致ERK与β5亚基之间发生关联。整合素αvβ6与ERK2之间的物理相互作用定义了整合素介导信号传导的新范例，并为癌症治疗提供了一个治疗靶点。
