Furin overexpression suppresses tumor growth and predicts a better postoperative disease-free survival in hepatocellular carcinoma.
Furin overexpression suppresses tumor growth and predicts a better postoperative disease-free survival in hepatocellular carcinoma.
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DOI：
10.1371/journal.pone.0040738
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发表时间：
2012
期刊：
影响因子：
3.7
通讯作者：
Yeh CT
中科院分区：
文献类型：
--
作者：
Huang YH;Lin KH;Liao CH;Lai MW;Tseng YH;Yeh CT
弗林蛋白酶是前蛋白转化酶家族的成员。它将几种生长调节蛋白加工成活性形式，这对肿瘤进展、转移和血管生成至关重要。弗林蛋白酶过表达可发生在肝癌中，并且先前的研究表明弗林蛋白酶过表达促进尾静脉异种移植模型中的HepG 2细胞侵袭。然而，弗林蛋白酶在肝细胞癌（HCC）中的表达的临床意义仍然未知。令人惊讶的是，在HCC患者的术后生存分析中，发现HCC组织中弗林蛋白酶表达的肿瘤/非肿瘤（T/N）比≥ 3.5预测更好的术后无病生存（DFS）（P = 0.010;对数秩检验）。 此外，皮下异种移植物实验证明了与模拟对照相比，弗林蛋白酶过表达的异种移植物（Huh 7-弗林蛋白酶）中肿瘤生长的显著抑制作用。向携带Huh 7-Furin异种移植物的小鼠施用用于抑制前蛋白转化酶活性的合成弗林蛋白酶抑制剂癸酰-Arg-Val-LyS-Arg-氯甲基酮（decRVKR-CMK）恢复了肿瘤生长的抑制作用。相反，向携带模拟Huh 7异种移植物的小鼠施用decRVKR-CMK显示生长速率没有变化。总之，弗林蛋白酶过表达抑制了皮下异种移植模型中HCC肿瘤的生长，并在临床分析中预测了更好的术后DFS。
Furin is a member of the pro-protein convertase family. It processes several growth regulatory proteins into their active forms, which are critical to tumor progression, metastasis, and angiogenesis. Furin over-expression could occur in liver cancer and a previous study showed that over-expression of furin promoted HepG2 cell invasion in tail vein xenograft models. However, the clinical relevance of furin expression in hepatocellular carcinoma (HCC) remained unknown. Surprisingly, in a postoperative survival analysis for HCC patients, it was found that the tumor/non-tumor (T/N) ratio of furin expression ≥ 3.5 in HCC tissues predicted a better postoperative disease-free survival (DFS) (P = 0.010; log-rank test). Furthermore, subcutaneous xenograft experiments demonstrated a significant suppression effect of tumor growth in the furin-overexpressed xenografts (Huh7-Furin) compared to the mock control. Administration of a synthetic furin inhibitor for inhibition of the pro-protein convertase activity, decanoyl-Arg-Val-Lys-Arg-chloromethylketone (decRVKR-CMK), to the Huh7-Furin xenograft bearing mice restored the repression effect of tumor growth. In contrast, administration of decRVKR-CMK to the mock Huh7 xenograft bearing mice showed no change in growth rate. In conclusion, furin overexpression inhibited HCC tumor growth in a subcutaneous xenograft model and predicted a better postoperative DFS in clinical analysis.
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影响因子：
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作者：
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