Abstract 2544: Overexpression of the Polo-like kinase 4 (PLK4) contribute to tumor metastasis

Abstract

Abstract The Polo-like kinase 4 (PLK4) is an important mitotic kinase that lies at the head of centriole duplication pathway. Aberration of PLK4's level in cancer cell often results in supernumery 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, knocking down PLK4 in 97L and HLE Hepatocellular Carcinoma (HCC) cell reduced their migration and growth rate. Overexpression of PLK4 in well-differentiated hepatoma HepG2 and Huh7 cell 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 how PLK4 contribute to cell migration, microtubule regrowth assay was carried out. The results indicating that PLK4 overexpressing cell had a higher rate of microtubule nucleation, which could contribute to directional movement of the cell. Further supporting that PLK4 contribute to HCC progression, we look into the clinical samples. Using qRT-PCR, we found PLK4 transcript is upregulated in a local cohort of HCC samples (n=48), 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. Suggesting targeted therapy against PLK4 might be useful in reducing tumor growth or metastasis. Citation Format: Yeung Sai Fung, Yick Pang Ching. Overexpression of the Polo-like kinase 4 (PLK4) contribute to tumor metastasis [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 2544.