Department of Biotechnology, Daegu University, Gyeongsan, Gyeongbuk 38453, Republic of Korea.
Department of Immunology, School of Medicine, Keimyung University, Dalseo-Gu, Daegu 704-701, Republic of Korea.
Pharmacol Ther. 2019 Jun;198:1-19. doi: 10.1016/j.pharmthera.2019.02.003. Epub 2019 Feb 11.
Cathepsins (CTS) are mainly lysosomal acid hydrolases extensively involved in the prognosis of different diseases, and having a distinct role in tumor progression by regulating cell proliferation, autophagy, angiogenesis, invasion, and metastasis. As all these processes conjunctively lead to cancer progression, their site-specific regulation might be beneficial for cancer treatment. CTS regulate activation of the proteolytic cascade and protein turnover, while extracellular CTS is involved in promoting extracellular matrix degradation and angiogenesis, thereby stimulating invasion and metastasis. Despite cancer regulation, the involvement of CTS in cellular adaptation toward chemotherapy and radiotherapy augments their therapeutic potential. However, lysosomal permeabilization mediated cytosolic translocation of CTS induces programmed cell death. This complex behavior of CTS generates the need to discuss the different aspects of CTS associated with cancer regulation. In this review, we mainly focused on the significance of each cathepsin in cancer signaling and their targeting which would provide noteworthy information in the context of cancer biology and therapeutics.
组织蛋白酶（CTS）主要是溶酶体酸性水解酶，广泛参与不同疾病的预后，通过调节细胞增殖、自噬、血管生成、侵袭和转移，在肿瘤进展中发挥独特作用。由于所有这些过程共同导致癌症进展，因此对其进行特定部位的调节可能对癌症治疗有益。CTS 调节蛋白水解级联和蛋白质周转的激活，而细胞外 CTS 参与促进细胞外基质降解和血管生成，从而刺激侵袭和转移。尽管癌症调控，CTS 在细胞对化疗和放疗的适应性中的参与增加了它们的治疗潜力。然而，溶酶体通透性介导的 CTS 胞质易位诱导程序性细胞死亡。CTS 的这种复杂行为需要讨论与癌症调控相关的 CTS 的不同方面。在这篇综述中，我们主要集中于每个组织蛋白酶在癌症信号中的重要性及其靶向性，这将在癌症生物学和治疗学方面提供有价值的信息。
