Department of Organic Chemistry, Medical University of Gdansk, Hallera 107, 80-416 Gdansk, Poland.
Department of Biology and Pharmaceutical Botany, Medical University of Gdansk, Hallera 107, 80-416 Gdansk, Poland.
Biochimie. 2018 Aug;151:85-106. doi: 10.1016/j.biochi.2018.05.023. Epub 2018 Jun 2.
Cysteine cathepsins (CTS), being involved in both physiological and pathological processes, play an important role in the human body. During the last 30 years, it has been shown that CTS are highly upregulated in a wide variety of cancer types although they have received a little attention as a potential therapeutic target as compared to serine or metalloproteinases. Studies on the increasing problem of neoplastic progression have revealed that secretion of cell-surface- and intracellular cysteine proteases is aberrant in tumor cells and has an impact on their growth, invasion, and metastasis by taking part in tumor angiogenesis, in apoptosis, and in events of inflammatory and immune responses. Considering the role of CTS in carcinogenesis, inhibition of these enzymes becomes an attractive strategy for cancer therapy. The downregulation of natural CTS inhibitors (CTSsis), such as cystatins, observed in various types of cancer, supports this claim. The intention of this review is to highlight the relationship of CTS with cancer and to present illustrations that explain how some of their inhibitors affect processes related to neoplastic progression.
半胱氨酸蛋白酶（CTS）参与生理和病理过程，在人体中发挥重要作用。在过去的 30 年中，已经表明 CTS 在多种癌症类型中高度上调，尽管与丝氨酸或金属蛋白酶相比，它们作为潜在的治疗靶点受到的关注较少。对肿瘤进展日益增加的问题的研究表明，肿瘤细胞中细胞表面和细胞内半胱氨酸蛋白酶的分泌异常，并通过参与肿瘤血管生成、细胞凋亡以及炎症和免疫反应事件，对其生长、侵袭和转移产生影响。鉴于 CTS 在致癌作用中的作用，抑制这些酶成为癌症治疗的一种有吸引力的策略。在各种类型的癌症中观察到天然 CTS 抑制剂（CTSsis）的下调，如胱抑素，支持了这一说法。本文的目的是强调 CTS 与癌症的关系，并提供说明，解释它们的一些抑制剂如何影响与肿瘤进展相关的过程。
