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越来越多的研究表明,基质金属蛋白酶(matrix metalloproteinases,MMPs)与肿瘤细胞上皮间质转化(epithelial-mes-enchymal transition,EMT)的关系密切。MMPs是间质细胞表型的特有蛋白之一,既可以作为EMT发生的一个重要标志物,又可以诱发EMT。MMPs诱导肿瘤细胞发生EMT的机制是一个复杂的网络,可能涉及多个信号通路,如介导Rac1b激活ROS释放通路、活化TGF-β通路、降解E-cadherin促使β-catenin入核通路等。鉴于MMPs是诱导EMT促进肿瘤转移的一个关键因素,靶向MMPs已成为临床防治肿瘤的一个新策略。因此MMPs抑制剂则是当前研究热点,目前,多达50多种MMPs抑制剂被列入临床治疗肿瘤的候选药物,但其中大部分的疗效并未得到肯定。缺乏特异性则是其主要原因,故靶向MMP-EMT途径的肿瘤治疗仍然面临着很大的挑战,不仅需要鉴定出涉及肿瘤进展、促进EMT的主要或单一MMP,而且需要开发出具有高度特异性、选择性的MMPs抑制剂。
More and more researches have shown that the relationship between matrix metalloproteinases (MMPs) and epithelial-mesodermal transition (EMT) is closely related. MMPs is one of the specific proteins of stromal cell phenotype, which can be used as an important marker of EMT, and can induce EMT. MMPs induced tumor cell EMT mechanism is a complex network that may involve multiple signaling pathways, such as Rac1b-mediated activation of ROS release pathway, activation of TGF-β pathway, degradation of E-cadherin promote β-catenin into the nuclear pathway. Given that MMPs are a key factor in inducing EMT to promote tumor metastasis, targeting MMPs has become a new strategy for clinical prevention and treatment of tumors. Therefore, MMPs inhibitors are the current research hot spots. At present, up to 50 kinds of MMPs inhibitors are included in the clinical treatment of tumor candidate drugs, but most of the curative effect has not been affirmed. Lack of specificity is the main reason for this, and therefore the treatment of tumors targeting the MMP-EMT pathway still poses a great challenge not only to identify the primary or single MMPs involved in tumor progression and promoting EMT, but also to develop antibodies that are highly specific Sexual, selective MMPs inhibitors.