Identification of KvLQT1 K+ channels as new regulators of non-small cell lung cancer cell proliferation and migration

Abstract

K+ channels, which are overexpressed in several cancers, have been identified as regulators of cell proliferation and migration, key processes in cancer development/propagation. Their role in lung cancer has not been studied extensively; but we showed previously that KvLQT1 channels are involved in cell migration, proliferation and repair of normal lung epithelial cells. We now investigated the role of these channels in lung cancer cell lines and their expression levels in human lung adenocarcinoma (AD) tissues. First, we observed that the wound-healing rates of A549 lung adenocarcinoma cell monolayers were reduced by clofilium and chromanol or after silencing with KvLQT1-specific siRNA. Dose-dependent decrease of A549 cell growth and cell accumulation in G0/G1 phase were seen after KvLQT1 inhibition. Clofilium also affected 2D and 3D migration of A549 cells. Similarly, H460 cell growth, migration and wound healing were diminished by this drug. Because K+ channel overexpression has been encountered in some cancers, we assessed KvLQT1 expression levels in tumor tissues from patients with lung AD. KvLQT1 protein expression in tumor samples was increased by 1.5- to 7-fold, compared to paired non-neoplastic tissues, in 17 of 26patients. In summary, our data reveal that KvLQT1 channel blockade efficiently reduces A549 and H460 cell proliferation and migration. Moreover, KvLQT1 overexpression in AD samples suggests that it could be a potential therapeutic target in lung cancer.