Activated PLK1 promotes the migration and invasion of polyploid giant cancer cells with daughter cells via β-catenin/STAT3 signaling pathway

The abundance of polyploid giant cancer cells (PGCCs) is correlated with malignant tumor progression. PGCCs divide asymmetrically to generate daughter cells with high invasive and migratory capacities. The objective of this study was to investigate the mechanism by which the overexpression of polo-like kinase 1 (PLK1) regulates the migration and invasion of PGCCs and their daughter cells (PDCs). In the present study, PGCC formation was induced by CoCl2 in Hct116 and LoVo cells. The mRNA expression and protein levels were detected using reverse transcription-quantitative PCR and western blotting, respectively. The regulatory relationships among related proteins were determined via small molecule inhibitors, transient small interfering RNA (siRNA) transfection, and coimmunoprecipitation. Our findings indicated that CoCl2 induces PGCC formation and produces progeny cells with increased invasive and metastatic abilities. PLK1 was expressed in PDCs and showed altered subcellular localization. In addition, aurora kinase A (AURKA) activated PLK1 by phosphorylating it at serine 137 and threonine 210. Activated PLK1 first stabilizes beta-catenin accumulation in the cytoplasm and subsequently promotes its entry into the nucleus. After entering the nucleus, beta-catenin promotes the accumulation of the tyrosine 705 site of signal transducer and activator of transcription 3 (pSTAT3-Tyr705), which promotes the downstream expression of target proteins, such as cyclin D1, matrix metallopeptidase 2 (MMP2) and c-MYC, and EMT-associated proteins as transcription factors. Furthermore, STAT3 and PLK1 form a feedback loop, allowing STAT3 to regulate PLK1 expression. In conclusion, PLK1 phosphorylation at different sites regulates the transcriptional function of pSTAT3-Tyr705 by promoting beta-catenin nuclear translocation. Furthermore, AURKA and STAT3 affected PLK1 expression.