Abstract 4611: The co-targeting of PLK1 and FoxM1 contributes to synergistic antitumor effects in PTC

Abstract

Abstract Polo-like Kinase 1 (PLK1) plays a key role in cell proliferation with vital regulatory functions in mitosis and cell survival. We investigated the expression of PLK1 protein in a large cohort of PTC patient’s samples and explored its functional role in PTC cell lines in vitro and in vivo. PLK1 overexpression was observed in 54% of all PTC and was significantly associated with aggressive clinico-pathological parameter and it was found to be independent prognostic marker for recurrence-free survival. PLK1 inhibition indeed inhibited cell proliferation and induced cell cycle arrest and apoptosis in PTC cell lines. Importantly, silencing of PLK1 decreases the self-renewal ability of spheroids generated from PTC cells. Immunoprecipitation analysis shows that PLK1 binds to FoxM1 and vice versa in vitro. Mechanistically, PLK1 knockdown suppresses FoxM1 expression, whereas inhibition of FoxM1 does not affect PLK1 expression, which suggests that PLK1 acts through the FoxM1 pathway. The combined inhibition of PLK1 with volasertib and FoxM1 with thiostrepton synergistically attenuated PTC cell growth in vitro and in vivo. Our findings suggest that co-targeting of PLK1 and FoxM1 could be a viable therapeutic strategy for treating patients with an aggressive subtype of PTC. Citation Format: Pratheeshkumar Poyil, Abdul K. Siraj, Divya Padmaja, Sandeep Kumar Parvathareddy, Saravanan Thangavel, Saif S. Al-Sobhi, Fouad Al-Dayel, Khawla S. Al-Kuraya. The co-targeting of PLK1 and FoxM1 contributes to synergistic antitumor effects in PTC [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 4611.