Centro de Investigaciones Médicas (CIM), Programa de Investigación Asociativa en Cáncer Gástrico (PIA-CG), Escuela de Medicina, Universidad de Talca, Talca 3460000, Chile.
Int J Mol Sci. 2018 Mar 29;19(4):1033. doi: 10.3390/ijms19041033.
TASK-3 potassium channels are believed to promote proliferation and survival of cancer cells, in part, by augmenting their resistance to both hypoxia and serum deprivation. While overexpression of TASK-3 is frequently observed in cancers, the understanding of its role and regulation during tumorigenesis remains incomplete. Here, we evaluated the effect of reducing the expression of TASK-3 in MDA-MB-231 and MCF-10F human mammary epithelial cell lines through small hairpin RNA (shRNA)-mediated knockdown. Our results show that knocking down TASK-3 in fully transformed MDA-MB-231 cells reduces proliferation, which was accompanied by an induction of cellular senescence and cell cycle arrest, with an upregulation of cyclin-dependent kinase (CDK) inhibitors p21 and p27. In non-tumorigenic MCF-10F cells, however, TASK-3 downregulation did not lead to senescence induction, although cell proliferation was impaired and an upregulation of CDK inhibitors was also evident. Our observations implicate TASK-3 as a critical factor in cell cycle progression and corroborate its potential as a therapeutic target in breast cancer treatment.
TASK-3 钾通道被认为通过增强其对缺氧和血清剥夺的抵抗力，促进癌细胞的增殖和存活。虽然 TASK-3 的过表达在癌症中经常被观察到，但对其在肿瘤发生过程中的作用和调节的理解仍然不完整。在这里，我们通过短发夹 RNA (shRNA)介导的敲低，评估了在 MDA-MB-231 和 MCF-10F 人乳腺上皮细胞系中降低 TASK-3 表达的效果。我们的结果表明，在完全转化的 MDA-MB-231 细胞中敲低 TASK-3 会降低增殖，这伴随着细胞衰老和细胞周期停滞的诱导，细胞周期蛋白依赖性激酶 (CDK) 抑制剂 p21 和 p27 的上调。然而，在非致瘤性 MCF-10F 细胞中，TASK-3 的下调并没有导致衰老的诱导，尽管细胞增殖受到损害，CDK 抑制剂的上调也很明显。我们的观察结果表明 TASK-3 是细胞周期进展的关键因素，并证实了其在乳腺癌治疗中的潜在治疗靶点。
