alpha 6 beta 4 and alpha 6 beta 1 integrins associate with ErbB-2 in human carcinoma cell lines
alpha 6 beta 4 and alpha 6 beta 1 integrins associate with ErbB-2 in human carcinoma cell lines
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DOI：
10.1006/excr.1997.3695
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发表时间：
1997-10-10
影响因子：
3.7
通讯作者：
Sacchi, A
中科院分区：
文献类型：
--
作者：
Falcioni, R;Antonini, A;Sacchi, A
生长因子调节整联蛋白介导的细胞粘附和运动，并且它们的受体被认为与整联蛋白受体共享介导细胞内信号传导的蛋白质。串话。这些受体之间的相互作用被认为在转化和肿瘤进展中起相关作用。为了突出生长因子和细胞粘附受体之间可能的相互作用，我们研究了整合素是否与肿瘤细胞中的酪氨酸激酶受体相关。通过亲和层析和免疫印迹分析纯化的免疫复合物，我们研究了层粘连蛋白受体（α 6 β 1和α 6 β 4）与ErbB-2酪氨酸激酶在人癌细胞系中的结合。我们证明了α 6 β 4和α 6 β 1整合素与ErbB-2在来自癌或过表达ErbB-2的NIH 3 T3细胞的裂解物中共沉淀。整合素介导的ErbB-2受体的激活表明这种关联在功能上有意义。事实上，用α 6整联蛋白亚基的单克隆抗体处理的癌细胞显示与整联蛋白共沉淀的ErbB-2-磷酸化分子的配体依赖性增加和DNA合成增加。还在过表达α 6 β 4受体和ErbB-2蛋白的NIH 3 T3细胞中研究了生长因子受体和整合素之间的相互作用。我们报告说，细胞过度表达这两种受体，但不是那些过度表达一个残废的ErbB-2，表现出增强的增殖率和侵袭力，进一步表明，α 6 β 4整合素和ErbB-2受体的相互作用可能有助于产生一个更恶性表型的癌细胞。(C)北京：科学出版社.
Growth factors modulate integrin-mediated cell adhesion and motility, and their receptors are thought to share proteins that mediate intracellular signaling with integrin receptors. The crosstalk. between these receptors is thought to play a relevant role in transformation and tumor progression. To highlight possible interactions between growth factors and cell adhesion receptors we investigated whether integrins associate with tyrosine kinase receptors in tumor cells. By affinity chromatography and Western blot analyses of purified immune complexes, we studied the association of laminin receptors (alpha 6 beta 1 and alpha 6 beta 4) with ErbB-2 tyrosine kinase in human carcinoma cell lines. We demonstrated that the alpha 6 beta 4 and alpha 6 beta 1 integrins coprecipitated with ErbB-2 in lysates from carcinoma or NIH3T3 cells overexpressing ErbB-2. Integrin-mediated activation of ErbB-2 receptors suggested that this association is functionally meaningful. Indeed, carcinoma cells treated with a monoclonal antibody to the alpha 6 integrin subunit showed a ligand-dependent increase of ErbB-2-phosphorylated molecules coprecipitated with integrins and an increased DNA synthesis. The interaction between growth factor receptors and integrins was also studied in NIH3T3 cells overexpressing alpha 6 beta 4 receptors and ErbB-2 protein. We report that cells overexpressing both receptors, but not those overexpressing a crippled ErbB-2, showed enhanced proliferation rates and invasiveness, further suggesting that alpha 6 beta 4 integrin and ErbB-2 receptor interaction might contribute to generate a more malignant phenotype in carcinoma cells. (C) 1997 Academic Press.