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Kv3.1 和 Kv3.4 参与癌细胞的迁移和侵袭。

Kv3.1 and Kv3.4, Are Involved in Cancer Cell Migration and Invasion.

机构信息

Laboratory of Veterinary Pharmacology, College of Veterinary Medicine and Research Institute for Veterinary Science, Seoul National University, Seoul 08826, Korea.

出版信息

Int J Mol Sci. 2018 Apr 2;19(4):1061. doi: 10.3390/ijms19041061.

DOI:10.3390/ijms19041061
PMID:29614836
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC5979479/
Abstract

Voltage-gated potassium (Kv) channels, including Kv3.1 and Kv3.4, are known as oxygen sensors, and their function in hypoxia has been well investigated. However, the relationship between Kv channels and tumor hypoxia has yet to be investigated. This study demonstrates that Kv3.1 and Kv3.4 are tumor hypoxia-related Kv channels involved in cancer cell migration and invasion. Kv3.1 and Kv3.4 protein expression in A549 and MDA-MB-231 cells increased in a cell density-dependent manner, and the pattern was similar to the expression patterns of hypoxia-inducible factor-1α (HIF-1α) and reactive oxygen species (ROS) according to cell density, whereas Kv3.3 protein expression did not change in A549 cells with an increase in cell density. The Kv3.1 and Kv3.4 blocker blood depressing substance (BDS) did not affect cell proliferation; instead, BDS inhibited cell migration and invasion. We found that BDS inhibited intracellular pH regulation and extracellular signal-regulated kinase (ERK) activation in A549 cells cultured at a high density, potentially resulting in BDS-induced inhibition of cell migration and invasion. Our data suggest that Kv3.1 and Kv3.4 might be new therapeutic targets for cancer metastasis.

摘要

电压门控钾 (Kv) 通道，包括 Kv3.1 和 Kv3.4，被认为是氧气传感器，其在缺氧条件下的功能已得到充分研究。然而，Kv 通道与肿瘤缺氧之间的关系尚未得到研究。本研究表明，Kv3.1 和 Kv3.4 是与肿瘤缺氧相关的 Kv 通道，参与癌细胞迁移和侵袭。A549 和 MDA-MB-231 细胞中 Kv3.1 和 Kv3.4 蛋白的表达随细胞密度呈依赖性增加，其表达模式与缺氧诱导因子-1α (HIF-1α) 和活性氧 (ROS) 的表达模式相似，而 Kv3.3 蛋白的表达在 A549 细胞中并未随细胞密度的增加而发生变化。Kv3.1 和 Kv3.4 阻断剂血抑素 (BDS) 不影响细胞增殖，反而抑制细胞迁移和侵袭。我们发现 BDS 抑制了高细胞密度培养的 A549 细胞内 pH 调节和细胞外信号调节激酶 (ERK) 的激活，可能导致 BDS 诱导的细胞迁移和侵袭抑制。我们的数据表明，Kv3.1 和 Kv3.4 可能是癌症转移的新治疗靶点。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5bda/5979479/e84e9810abe4/ijms-19-01061-g007.jpg
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