Mammary-derived growth inhibitor (MDGI) interacts with integrin α-subunits and suppresses integrin activity and invasion
Mammary-derived growth inhibitor (MDGI) interacts with integrin α-subunits and suppresses integrin activity and invasion
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DOI：
10.1038/onc.2010.376
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发表时间：
2010-12-01
期刊：
影响因子：
8
通讯作者：
Ivaska, J.
中科院分区：
文献类型：
--
作者：
Nevo, J.;Mai, A.;Ivaska, J.
与癌症相关的大多数死亡率是由于原发肿瘤转移的形成。不同整合素异源二聚体介导的粘附在细胞迁移和侵袭过程中起重要作用。已知蛋白质与β 1-整联蛋白胞质尾的相互作用影响整联蛋白对细胞外配体的亲和力，但α-亚基胞质尾的调节结合配偶体仍然难以捉摸。在这项研究中，我们表明，乳腺衍生的生长抑制剂（MDGI）（也称为FABP-3或H-FABP）直接结合到整合素α亚基的细胞质尾区，其表达抑制整合素活性。在乳腺癌细胞系中，MDGI表达与整合素活性构象的抑制相关。这导致整合素与I型胶原和纤连蛋白的粘附减少，并抑制细胞迁移和侵袭。在1331例乳腺癌患者的组织芯片中，MDGI阳性肿瘤患者的10年无远处转移生存率高于MDGI阴性肿瘤患者。我们的数据表明，MDGI是整合素α亚基的一种新型相互作用伙伴，其表达调节整合素活性并抑制乳腺癌患者的细胞侵袭。MDGI表达的保留与良好的预后相关。Oncogene（2010）29，6452-6463; doi：10.1038/onc.2010.376; 2010年8月30日在线发表
The majority of mortality associated with cancer is due to formation of metastases from the primary tumor. Adhesion mediated by different integrin heterodimers has an important role during cell migration and invasion. Protein interactions with the beta 1-integrin cytoplasmic tail are known to influence integrin affinity for extracellular ligands, but regulating binding partners for the alpha-subunit cytoplasmic tails have remained elusive. In this study, we show that mammary-derived growth inhibitor (MDGI) (also known as FABP-3 or H-FABP) binds directly to the cytoplasmic tail of integrin alpha-subunits and its expression inhibits integrin activity. In breast cancer cell lines, MDGI expression correlates with suppression of the active conformation of integrins. This results in reduced integrin adhesion to type I collagen and fibronectin and inhibition of cell migration and invasion. In tissue microarray of 1331 breast cancer patients, patients with MDGI-positive tumors had more favorable 10-year distant disease-free survival compared with patients with MDGI-negative tumors. Our data indicate that MDGI is a novel interacting partner for integrin alpha-subunits, and its expression modulates integrin activity and suppresses cell invasion in breast cancer patients. Retained MDGI expression is associated with favorable prognosis. Oncogene (2010) 29, 6452-6463; doi:10.1038/onc.2010.376; published online 30 August 2010