J Cancer 2017; 8(19):4125-4140. doi:10.7150/jca.21802
Decreased KPNB1 Expression is Induced by PLK1 Inhibition and Leads to Apoptosis in Lung Adenocarcinoma
1. Department of Computational Biology and Medical Sciences, Graduate School of Frontier Sciences, The University of Tokyo, Minato-ku, Tokyo 108-8639, Japan;
2. Department of Computational Biology and Medical Sciences, Graduate School of Frontier Sciences, The University of Tokyo, Kashiwa, Chiba 277-8562, Japan.
Sekimoto N, Suzuki Y, Sugano S. Decreased KPNB1 Expression is Induced by PLK1 Inhibition and Leads to Apoptosis in Lung Adenocarcinoma. J Cancer 2017; 8(19):4125-4140. doi:10.7150/jca.21802. Available from http://www.jcancer.org/v08p4125.htm
Lung cancer is a major cause of death worldwide, with lung adenocarcinoma being the most frequently diagnosed subtype in Japan. Finding the target of an anticancer drug can improve lung adenocarcinoma treatments. Polo-like kinase 1 (PLK1) is an essential mitotic kinase in mitotic progression, and PLK1 inhibition induces cell cycle arrest and apoptosis in tumor cells. In addition, a variety of PLK1 inhibitors have been identified for cancer treatments. In this study, we looked for the target gene of the anticancer drug that has synergy with PLK1 inhibitors. We identified karyopherin beta 1 (KPNB1) as a possible target for lung adenocarcinoma treatment. We found that PLK1 inhibition decreased KPNB1 expression in lung adenocarcinoma cells and KPNB1 depletion inhibited cell proliferation via apoptosis. The same apoptosis signaling pathway may be activated because the expression of common apoptosis-related genes was decreased by PLK1 and KPNB1 silencing; however, the time course of cell growth inhibition was somewhat different. Cell cycle analysis showed that KPNB1 depletion increased the proportion of cells at the G0/G1 phase, although cells also accumulated at the G2/M phase in PLK1-depleted cells. Our findings suggest that decreased KPNB1 expression may be associated with the apoptosis induced by PLK1 inhibition.
Keywords: PLK1, KPNB1, Lung adenocarcinoma, Apoptosis.