Lysyl Oxidase Isoforms and Potential Therapeutic Opportunities for Fibrosis and Cancer.
Lysyl Oxidase Isoforms and Potential Therapeutic Opportunities for Fibrosis and Cancer.
复制标题
DOI：
10.1517/14728222.2016.1151003
复制
发表时间：
2016-08
影响因子：
5.8
通讯作者：
Trackman PC
中科院分区：
文献类型：
--
作者：
Trackman PC
赖氨酰氧化酶家族的酶通常被认为是结缔组织成熟所需的，其通过氧化弹性蛋白中的赖氨酸残基以及胶原蛋白前体中的赖氨酸和羟赖氨酸残基来实现。所产生的醛然后参与交联形成，这是正常结缔组织完整性所必需的。这些酶的生物学功能超出了这种基本的生物合成作用，有助于血管生成，细胞增殖和细胞分化。赖氨酰氧化酶的失调发生在多种病理学中，包括纤维化、原发性和转移性癌症以及各种组织中的糖尿病并发症。这篇综述总结了赖氨酰氧化酶在病理学中的新作用的主要发现，并强调了一些潜在的治疗方法，正在开发和源于这些新的发现。关于这个蛋白质家族的新生物学功能的机制以及关于独立于其催化酶活性的功能的基本问题仍然存在。然而，在开发异构体特异性药理学抑制剂、潜在的治疗性抗体以及获得对肿瘤抑制剂和转移促进活性的更多理解方面正在取得进展。最终，这可能会导致新的治疗药物。
The lysyl oxidase family of enzymes is classically known as being required for connective tissue maturation by oxidizing lysine residues in elastin and lysine and hydroxylysine residues in collagen precursors. The resulting aldehydes then participate in cross-link formation, which is required for normal connective tissue integrity. These enzymes have biological functions that extend beyond this fundamental biosynthetic role, with contributions to angiogenesis, cell proliferation, and cell differentiation. Dysregulation of lysyl oxidases occurs in multiple pathologies including fibrosis, primary and metastatic cancers, and complications of diabetes in a variety of tissues. This review summarizes the major findings of novel roles for lysyl oxidases in pathologies, and highlights some of the potential therapeutic approaches that are in development and which stem from these new findings. Fundamental questions remain regarding the mechanisms of novel biological functions of this family of proteins, and regarding functions that are independent of their catalytic enzyme activity. However, progress is underway in the development of isoform-specific pharmacologic inhibitors, potential therapeutic antibodies and gaining an increased understanding of both tumor suppressor and metastasis promotion activities. Ultimately, this is likely to lead to novel therapeutic agents.