Microbiome Convergence Research Center, Korea Research Institute of Bioscience and Biotechnology, Daejon, 34141, Korea.
Department of Functional Genomics, Korea University of Science and Technology, Daejon, 34113, Korea.
Exp Mol Med. 2023 Apr;55(4):716-724. doi: 10.1038/s12276-023-00975-5. Epub 2023 Apr 3.
Proteases are involved in almost all biological processes, implying their importance for both health and pathological conditions. Dysregulation of proteases is a key event in cancer. Initially, research identified their role in invasion and metastasis, but more recent studies have shown that proteases are involved in all stages of cancer development and progression, both directly through proteolytic activity and indirectly via regulation of cellular signaling and functions. Over the past two decades, a novel subfamily of serine proteases called type II transmembrane serine proteases (TTSPs) has been identified. Many TTSPs are overexpressed by a variety of tumors and are potential novel markers of tumor development and progression; these TTSPs are possible molecular targets for anticancer therapeutics. The transmembrane protease serine 4 (TMPRSS4), a member of the TTSP family, is upregulated in pancreatic, colorectal, gastric, lung, thyroid, prostate, and several other cancers; indeed, elevated expression of TMPRSS4 often correlates with poor prognosis. Based on its broad expression profile in cancer, TMPRSS4 has been the focus of attention in anticancer research. This review summarizes up-to-date information regarding the expression, regulation, and clinical relevance of TMPRSS4, as well as its role in pathological contexts, particularly in cancer. It also provides a general overview of epithelial-mesenchymal transition and TTSPs.
蛋白酶几乎参与所有的生物过程，这意味着它们对健康和病理状况都很重要。蛋白酶的失调是癌症的一个关键事件。最初的研究确定了它们在侵袭和转移中的作用，但最近的研究表明，蛋白酶直接通过蛋白水解活性以及通过调节细胞信号和功能，参与了癌症发展和进展的所有阶段。在过去的二十年中，已经鉴定出一种新型的丝氨酸蛋白酶亚家族，称为 II 型跨膜丝氨酸蛋白酶（TTSPs）。许多 TTSPs 被各种肿瘤过度表达，是肿瘤发展和进展的潜在新标志物；这些 TTSPs 可能是抗癌治疗的分子靶点。跨膜蛋白酶丝氨酸 4（TMPRSS4）是 TTSP 家族的一员，在胰腺、结直肠、胃、肺、甲状腺、前列腺和其他几种癌症中上调；事实上，TMPRSS4 的高表达通常与预后不良相关。基于其在癌症中的广泛表达谱，TMPRSS4 一直是抗癌研究的焦点。这篇综述总结了有关 TMPRSS4 的表达、调节和临床相关性的最新信息，以及它在病理情况下，特别是在癌症中的作用。它还提供了上皮-间充质转化和 TTSPs 的概述。
