钙整合素结合蛋白1与肿瘤研究进展  

Research Advances of Calcium-and Integrin-binding Protein 1 in Tumors

作　　者：惠玲[1] 王方[2] 

机构地区：[1]兰州军区兰州总医院医学实验中心甘肃省干细胞与基因药物重点实验室,兰州730050 [2]兰州军区兰州总医院安宁分院感染科,兰州730070

出　　处：《中国医学科学院学报》2017年第5期727-732,共6页Acta Academiae Medicinae Sinicae

基　　金：国家自然科学基金面上项目(81372177);甘肃省自然科学基金(1107RJZA106;1308RJZA284)和全军医药卫生科研基金(CLZ15JA01)~~

摘　　要：钙整合素结合蛋白1(CIB1)是一个含有EF-hand结构域的钙结合蛋白,可通过与不同信号分子的结合在多种生物学过程中发挥作用,参与调节细胞存活、增殖、黏附、迁移、血管新生等多种肿瘤特征性生物学过程。CIB1还能通过调节肿瘤相关的细胞外信号调节激酶1/2(ERK1/2)、磷脂酰肌醇3激酶(PI-3K)/v-AKT小鼠胸腺瘤病毒癌基因同源物信号通路促进细胞增殖和存活,或通过Src-家族酪氨酸激酶、蛋白激酶C、PI-3K和ERK1/2介导信号通路的激活促进细胞迁移。研究显示,CIB1能通过抑制丝苏氨酸蛋白激酶家族的polo样激酶3活性抑制细胞增殖;通过结合并激活p21激活激酶1抑制细胞迁移。尤其是在部分乳腺癌中CIB1的非癌基因成瘾的特性,使得CIB1有可能成为肿瘤靶向治疗的靶点之一。此外,CIB1在心肌肥大、耳聋、男性不育等疾病发生过程中也发挥至关重要的作用,因此对CIB1功能的研究有重要的临床意义。本文总结了CIB1近几年在肿瘤方面的研究进展。Calcium-and integrin-binding protein 1( CIB1),a member of calcium binding protein containing EF-hand domain,has been shown to bind a variety of signaling proteins. Interaction of CIB1 with its various binding partners provides valuable insight into potential mechanisms by which CIB1 may regulate diverse tumors characteristic biological process that range from adhesion,migration, cell survival, proliferation, and angiogenesis. CIB1 has also been implicated in both the increase and decrease of cell proliferation. CIB1 promoted cell proliferation and survival by adjusted tumor-associated extracellular regulated protein kinases 1/2( ERK1/2),phosphatidylinositol 3 kinase( PI-3 K)/v-akt murine thymoma viral oncogene homolog-dependent signaling pathway,or increased cell migration by activating Src family kinases,protein kinase C,PI-3 K,and ERK 1/2-mediated signaling pathway. CIB1 inhibited cell proliferation through inhibiting polo-like kinases 3( PLK3) activity. It also inhibits cell migration by binding to and activating p21-activated kinase 1. Especially a large subset of triple-negative breast cancer may display non-oncogene addiction to CIB1,a phenomenon in which cancer cells require,or become ‘addicted'to a non-mutated,non-overexpressed gene/protein that is nonetheless essential to maintain oncogenic signaling pathways,and implicate CIB1 as a novel drug target in tumors. Additionally,CIB1 plays a role in such pathological processes as cardiac hypertrophy,deafness,and male infertility. Research on CIB1 function has important clinical significance. In this review,we discussed current understanding of CIB1 in human tumors.

关 键 词：钙整合素结合蛋白 黏附 肿瘤 增殖 迁移 

分 类 号：Q71[生物学—分子生物学]