文章：

KCNF1通过调控ITGB4表达促进肺癌发生

KCNF1 promotes lung cancer by modulating ITGB4 expression 

原文发布日期：2022-11-16 

英文摘要：

Lung cancer continues to be the leading cause of cancer death in the United States. Despite recent advances, the five-year survival rate for lung cancer compared to other cancers still remains fairly low. The discovery of molecular targets for lung cancer is key to the development of new approaches and therapies. Electrically silent voltage-gated potassium channel (KvS) subfamilies, which are unable to form functional homotetramers, are implicated in cell-cycle progression, cell proliferation and tumorigenesis. Here, we analyzed the expression of KvS subfamilies in human lung tumors and identified that potassium voltage-gated channel subfamily F member 1 (KCNF1) was up-regulated in non-small cell lung cancer (NSCLC). Silencing of KCNF1 in NSCLC cell lines reduced cell proliferation and tumor progression in mouse xenografts, re-established the integrity of the basement membrane, and enhanced cisplatin sensitivity. KCNF1 was predominately localized in the nucleoplasm and likely mediated its functions in an ion-independent manner. We identified integrin β4 subunit (ITGB4) as a downstream target for KCNF1. Our findings suggest that KCNF1 promotes lung cancer by enhancing ITGB4 signaling and implicate KCNF1 as a novel therapeutic target for lung cancer. 

摘要翻译： 

肺癌仍是美国癌症死亡的首要原因。尽管近期取得了一些进展，但与其他癌症相比，肺癌的五年生存率仍然较低。肺癌分子靶点的发现对于开发新方法和新疗法至关重要。电沉默电压门控钾通道（KvS）亚家族无法形成功能性同源四聚体，与细胞周期进程、细胞增殖和肿瘤发生密切相关。本研究分析了人类肺部肿瘤中KvS亚家族的表达，发现钾电压门控通道F亚家族成员1（KCNF1）在非小细胞肺癌（NSCLC）中表达上调。在NSCLC细胞系中沉默KCNF1可抑制细胞增殖和小鼠异种移植瘤的进展，重建基底膜完整性，并增强顺铂敏感性。KCNF1主要定位于核质，可能以非离子依赖方式发挥功能。我们发现整合素β4亚基（ITGB4）是KCNF1的下游靶点。研究结果表明KCNF1通过增强ITGB4信号传导促进肺癌发展，提示KCNF1可作为肺癌治疗的新靶点。

原文链接：

KCNF1 promotes lung cancer by modulating ITGB4 expression