Expression Alteration And Function Analysis Of PLK1 In Esophageal Squamous Cell Carcinoma

Polo-like kinase 1(PLK1) is one of the serine/threonine kinases involved in centrosome maturation,chromosome segregation and mitotic exit.PLK1 is frequently overexpressed in various kinds of human tumors.16p12 encompassing PLK1 gene has been previously identified as a common amplified region in esophageal squamous cell carcinoma(ESCC).The present study is to investigate the expression change of PLK1 in ESCC and the underlying molecular mechanisms through which PLK1 takes part in esophageal carcinogenesis and malignant development.Immunohistochemistry in 155 ESCC and adjacent normal tissues showed that PLK1 expression was considerably increased in tumors compared with that in normal epithelia.PLK1 overexpression was significantly associated with regional lymph node metastasis(P=0.001) and tumor stage(P=0.033).The prognosis of patients with PLK1-positive tumors was significantly worse than that with PLK1-negative (P=0.001).Multivariate survival analysis showed that PLK1 was an independent prognostic factor(RP=4.921,P=0.011).Amplification of the locus RP11-141E3 containing PLK1 gene was observed in 37.5%of tumors by fluorescence in situ hybridization,suggesting that gene amplification was the mechanism underlying PLK1 overexpression in a part of esophageal carcinomas.RNAi-mediated knockdown of PLK1 dramatically suppressed cell proliferation and resulted in apoptosis.Depletion of PLK1 activated the mitochondrial apoptotic pathway,which was substantiated by loss of mitochondrial membrane potential, reduction of survivin,Mcl-1 and Bcl-2,activation of caspase-9 and caspase-3 as well as cleavage of poly(ADP-ribose) polymerase(PARP).Co-immunoprecipitation and confocal microscopy displayed that PLK1 was associated with survivin andα-catenin.These data suggest that PLK1 plays a part in adhesion,differentiation and migration of cells.Survivin is probably involved in anti-apoptotic function of PLK1. PLK1 might be a useful prognostic marker and a potential therapeutic target for ESCC.