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Abstract：
Cathepsin C (CTSC), also known as dipeptidyl peptidase I, is a cathepsin with lysosomal exocysteine protease activity and a central coordinator for the activation of neutrophil-derived serine proteases in the lysosomes of neutrophils. Although the role of CTSC in various cancers, including liver and breast cancers, has recently been reported, its role in non-small cell lung cancer (NSCLC) is largely unknown. This study aimed to investigate the functional role of CTSC in NSCLC and the molecular mechanisms underlying CTSC involvement in disease progression. CTSC overexpression markedly enhanced the growth, motility, and invasiveness of NSCLC cells in vitro and in vivo. CTSC knockdown using shRNA in NSCLC cells reversed the migratory and invasive behavior of NSCLC cells. CTSC also induced epithelial-mesenchymal transition through the Yes-associated protein signaling pathway. In addition, our analyses of clinical samples confirmed that high CTSC expression was associated with lymph node metastasis and recurrence in lung adenocarcinoma. In conclusion, CTSC plays an important role in the progression of NSCLC. Thus, targeting CTSC may be a promising treatment option for patients with NSCLC.
摘要：
组织蛋白酶C(CTSC),也被称为二肽基肽酶I，是具有溶酶体外半胱氨酸蛋白酶活性的组织蛋白酶，并且是激活嗜中性粒细胞溶酶体中嗜中性粒细胞衍生的丝氨酸蛋白酶的中心协调器。虽然CTSC在各种癌症中的作用，包括肝癌和乳腺癌,最近有报道称，其在非小细胞肺癌(NSCLC)中的作用尚不清楚.本研究旨在探讨CTSC在NSCLC中的功能作用以及CTSC参与疾病进展的分子机制。CTSC过表达显着增强了生长，运动性,NSCLC细胞的体外和体内侵袭性。在NSCLC细胞中使用shRNA的CTSC敲除逆转了NSCLC细胞的迁移和侵袭行为。CTSC还通过Yes相关蛋白信号通路诱导上皮-间质转化。此外,我们对临床样本的分析证实,在肺腺癌中,CTSC高表达与淋巴结转移和复发相关.总之,CTSC在NSCLC的进展中起着重要作用。因此，靶向CTSC可能是NSCLC患者有希望的治疗选择.
