How, with whom and when: an overview of CD147-mediated regulatory networks influencing matrix metalloproteinase activity.
How, with whom and when: an overview of CD147-mediated regulatory networks influencing matrix metalloproteinase activity.
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DOI：
10.1042/bsr20150256
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发表时间：
2015-11-24
影响因子：
4
通讯作者：
Toole BP
中科院分区：
文献类型：
--
作者：
Grass GD;Toole BP
基质金属蛋白酶(MMPs)由23个锌依赖酶家族组成，参与多种病理生理过程。在癌症中，MMPs参与了从肿瘤起始到建立远处转移的过程。复杂的信号和蛋白质转运网络调节基质金属蛋白酶的合成、细胞表面的呈递和释放。早期试图干扰患者体内基质金属蛋白酶活性的尝试已被证明是无法忍受的，且临床疗效平平；因此，靶向调节基质金属蛋白酶活性的辅助蛋白可能是一种有用的治疗方法。细胞外基质金属蛋白酶诱导物(EMMPRIN)最初被认为是肺癌细胞上存在的一种刺激成纤维细胞产生胶原酶(MMP-1)的因子。随后的研究表明，EMMPRIN与其他几种蛋白质因子是相同的，包括basigin(BSG)，它们现在都被普遍称为CD147。CD147通过同亲/异亲细胞相互作用、囊泡脱落或细胞自主过程，在不同的环境中调节可溶性和膜结合的[膜型MMPs(MT-MMPs)]的合成和活性。CD147还参与炎症、营养和药物转运蛋白活性、微生物病理和发育过程。尽管已有数百篇文献证明了CD147对基质金属蛋白酶的调节作用，但调控这一过程的分子基础尚未完全阐明。本综述总结了我们目前对影响CD147生物学的复杂调控系统的了解，并提供了一个了解CD147如何影响基质金属蛋白酶活性的框架。
Matrix metalloproteinases (MMPs) comprise a family of 23 zinc-dependent enzymes involved in various pathologic and physiologic processes. In cancer, MMPs contribute to processes from tumour initiation to establishment of distant metastases. Complex signalling and protein transport networks regulate MMP synthesis, cell surface presentation and release. Earlier attempts to disrupt MMP activity in patients have proven to be intolerable and with underwhelming clinical efficacy; thus targeting ancillary proteins that regulate MMP activity may be a useful therapeutic approach. Extracellular matrix metalloproteinase inducer (EMMPRIN) was originally characterized as a factor present on lung cancer cells, which stimulated collagenase (MMP-1) production in fibroblasts. Subsequent studies demonstrated that EMMPRIN was identical with several other protein factors, including basigin (Bsg), all of which are now commonly termed CD147. CD147 modulates the synthesis and activity of soluble and membrane-bound [membrane-type MMPs (MT-MMPs)] in various contexts via homophilic/heterophilic cell interactions, vesicular shedding or cell-autonomous processes. CD147 also participates in inflammation, nutrient and drug transporter activity, microbial pathology and developmental processes. Despite the hundreds of manuscripts demonstrating CD147-mediated MMP regulation, the molecular underpinnings governing this process have not been fully elucidated. The present review summarizes our present knowledge of the complex regulatory systems influencing CD147 biology and provides a framework to understand how CD147 may influence MMP activity.