Targeting proprotein convertases in furin-rich lung cancer cells results in decreased in vitro and in vivo growth
Targeting proprotein convertases in furin-rich lung cancer cells results in decreased in vitro and in vivo growth
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DOI：
10.1002/mc.22550
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发表时间：
2017-03-01
影响因子：
4.6
通讯作者：
Klein-Szanto, Andres J.
中科院分区：
文献类型：
--
作者：
Bassi, Daniel E.;Zhang, Jirong;Klein-Szanto, Andres J.
前蛋白转化酶 (PC) 是一种丝氨酸蛋白酶，在多种非活性蛋白质翻译后加工成活性蛋白质（包括许多在癌症发生和进展中至关重要的底物）过程中发挥着积极作用。弗林蛋白酶 (PCSKC3) 是该家族中经过深入研究的成员，在许多人类和实验恶性肿瘤中过度表达。在本次通讯中，我们用 PC 抑制剂 CMK（癸酰基-精氨酸-缬氨酸-赖氨酸-精氨酸-氯甲基酮）治疗了两种弗林蛋白酶过度表达的非小细胞癌 (NSCLC) 细胞系（Calu-6 和 HOP-62）。这导致 IGF-1R 加工减少，同时两个 NSCLC 系的细胞增殖减少。类似地，两种细胞系的皮下异种移植物的生长均被相同药物的体内治疗部分抑制。这些观察结果表明 PC 抑制剂在癌症治疗中的潜在作用。 (C) 2016 年 Wiley 期刊公司。
Proprotein convertases (PCs) are serine proteases with an active role in the post-translational processing of numerous inactive proteins to active proteins including many substrates of paramount importance in cancer development and progression. Furin (PCSKC3), a well-studied member of this family, is overexpressed in numerous human and experimental malignancies. In the present communication, we treated two furin-overexpressing non-small cell carcinoma (NSCLC) cell lines (Calu-6 and HOP-62) with the PC inhibitor CMK (Decanoyl-Arg-Val-Lys-Arg-chloromethylketone). This resulted in a diminished IGF-1R processing and a simultaneous decrease in cell proliferation of two NSCLC lines. Similarly, growth of subcutaneous xenografts of both cell lines, were partially inhibited by an in vivo treatment with the same drug. These observations point to a potential role of PC inhibitors in cancer therapy. (C) 2016 Wiley Periodicals, Inc.