Jiangsu Key Laboratory of Drug Screening, China Pharmaceutical University, Nanjing, Jiangsu, China.
Department of Spine Surgery, The Third Affiliated Hospital, Sun Yat-sen University, Guangzhou, China.
Biomed Pharmacother. 2017 Jun;90:670-676. doi: 10.1016/j.biopha.2017.04.023. Epub 2017 Apr 14.
Collagen is not only the most abundant protein providing the scaffold for assembly of the extracellular matrix (ECM), but also considered to be the "highway" for cancer cell migration and invasion depending on the different collagen organizations. The accumulation of stabilized collagen is enhanced by different covalent collagen cross-links, lysyl hydroxylases 2 (encoded by the PLOD2 gene) is the key enzyme mediating the formation of the stabilized collagen cross-link. Interestingly, PLOD2 is overexpressed in different cancers and closely related to a poor prognosis. To the best of our knowledge, only the mechanisms of PLOD2 regulated by HIF-1α, TGF-β and microRNA-26a/b have been elaborated. In addition, several pharmacologic inhibitors of PLOD2 have been confirmed to have an anti-metastasis effect. However, there have been no reviews about PLOD2 in cancer research published thus far. In brief, this review about PLOD2 will describe the function, regulatory mechanism, and the inhibitors of PLOD2 in cancer, suggesting the credible clinical evaluation of a prognostic signature in pathological examination and the possible development of therapeutic strategies targeting PLOD2 in the future.
胶原蛋白不仅是提供细胞外基质(ECM)组装支架的最丰富的蛋白质,而且还被认为是癌细胞迁移和侵袭的“高速公路”,这取决于不同的胶原蛋白组织。不同的共价胶原蛋白交联会增强稳定的胶原蛋白的积累,赖氨酰羟化酶 2(由 PLOD2 基因编码)是介导稳定胶原蛋白交联形成的关键酶。有趣的是,PLOD2 在不同的癌症中过度表达,并且与预后不良密切相关。据我们所知,只有 HIF-1α、TGF-β 和 microRNA-26a/b 调节 PLOD2 的机制得到了阐述。此外,已经证实几种 PLOD2 的药理学抑制剂具有抗转移作用。然而,迄今为止,关于癌症研究中的 PLOD2 尚未有综述发表。简而言之,关于 PLOD2 的这篇综述将描述 PLOD2 在癌症中的功能、调节机制和抑制剂,提示在病理检查中对预后标志物进行可信的临床评估,并可能在未来针对 PLOD2 开发治疗策略。