Overexpression of the Polo-Like- Kinase 4 (PLK4) contribute to tumor metastasis

Abstract

The Polo‐Like Kinase 4 (PLK4) is an important mitotic kinase that plays a critical role in centriole duplication pathway. Aberrant PLK4's level in cancer cell often results in supernumerary centrosome. PLK4 transcripts was upregulated in a number of cancers including breast, colon gastric and lung cancer, and PLK4 overexpression had been linked to chemoresistance and cancer metastasis. In our preliminary data, knockdown of PLK4 in hepatocellular carcinoma (HCC) cell lines, 97L and HLE, reduced their migration and growth rates. Overexpression of PLK4 in well‐differentiated hepatoma cell lines, HepG2 and Huh7, showed enhancement in migration. Centrinone B, a highly potent PLK4 inhibitor, inhibits HCC cells' colony‐forming ability and wound healing rate. To gain the insight into the mechanism by which PLK4 contributes to cell migration, microtubule regrowth assay was carried out. The results indicated that PLK4 overexpressing cell had a higher rate of microtubule nucleation, which could contribute to directional movement of the cell. To evaluate the effect of PLK4 in HCC progression, we examine the expression of PLK4 in clinical samples. Using qRT‐PCR, we found PLK4 transcript is upregulated in a local cohort of HCC samples (n=48) and we also confirmed that PLK4 is upregulated in the TCGA and two GEO available datasets. Data from the cancer dependency map showed PLK4 is a common essential gene in a panel of HCC cell line. Taken together, these date suggest that targeting PLK4 might be useful in reducing tumor growth or metastasis.