Department of Cell Biology, School of Basic Medical Sciences, Southern Medical University, Guangzhou 510515, China.
Department of Dermatology, Guangdong Provincial People’s Hospital, Guangdong Academy of Medical Sciences, Guangzhou 510080, China.
Aging (Albany NY). 2023 Dec 8;15(23):13961-13979. doi: 10.18632/aging.205278.
Cathepsin V (CTSV) is a cysteine cathepsin protease that plays a crucial role in extracellular matrix degradation. CTSV is correlated with poor prognosis in various cancers, but the underlying mechanism remains elusive. Here, we observed that CSTV is upregulated in lung cancer and is a poor prognosis factor for lung cancer. CTSV acts as a driver in the metastasis of lung cancer both and . CTSV promotes lung cancer metastasis by downregulating adhesion molecules, including fibronectin, E-cadherin, and N-cadherin. Our data revealed that CTSV functions by mediating the fragmentation of fibronectin, E-cadherin, and N-cadherin in cleavage, remodeling the extracellular matrix (ECM). The rationally designed antibody targeting CTSV blocks its cleaving ability towards fibronectin, E-cadherin, and N-cadherin, suppressing migration and invasion. Furthermore, we found that CTSV expression is negatively correlated with immune cell infiltration and immune scores and inhibits T cell activity. Targeting CTSV with specific antibodies effectively suppressed lung cancer metastasis in a mouse model. Our study demonstrates the critical role of CTSV in the immunity and metastasis of lung cancer, suggesting that the CTSV-targeting approach is a promising strategy for lung cancer.
组织蛋白酶 V(CTSV)是一种半胱氨酸组织蛋白酶蛋白酶,在细胞外基质降解中发挥着关键作用。CTSV 与各种癌症的预后不良相关,但潜在的机制仍不清楚。在这里,我们观察到 CTSV 在肺癌中上调,是肺癌的预后不良因素。CTSV 既是肺癌转移的驱动因素,也是 。CTSV 通过下调包括纤连蛋白、E-钙黏蛋白和 N-钙黏蛋白在内的黏附分子来促进肺癌转移。我们的数据表明,CTSV 通过介导纤连蛋白、E-钙黏蛋白和 N-钙黏蛋白的片段化来发挥作用,重塑细胞外基质(ECM)。针对 CTSV 的合理设计的抗体可以阻断其对纤连蛋白、E-钙黏蛋白和 N-钙黏蛋白的切割能力,从而抑制迁移和侵袭。此外,我们发现 CTSV 表达与免疫细胞浸润和免疫评分呈负相关,并抑制 T 细胞活性。用特异性抗体靶向 CTSV 可有效抑制小鼠模型中的肺癌转移。我们的研究表明 CTSV 在肺癌的免疫和转移中起着关键作用,提示针对 CTSV 的方法是治疗肺癌的一种有前途的策略。