The Role of Polo-Like Kinase 1 in Regulating the Forkhead Box Family Transcription Factors

Abstract

Polo-like kinase 1 (PLK1) is a serine/threonine kinase with more than 600 phosphorylation substrates through which it regulates many biological processes, including mitosis, apoptosis, metabolism, RNA processing, vesicle transport, and G2 DNA-damage checkpoint recovery, among others. Among the many PLK1 targets are members of the FOX family of transcription factors (FOX TFs), including FOXM1, FOXO1, FOXO3, and FOXK1. FOXM1 and FOXK1 have critical oncogenic roles in cancer through their antagonism of apoptotic signals and their promotion of cell proliferation, metastasis, angiogenesis, and therapeutic resistance. In contrast, FOXO1 and FOXO3 have been identified to have broad functions in maintaining cellular homeostasis. In this review, we discuss PLK1-mediated regulation of FOX TFs, highlighting the effects of PLK1 on the activity and stability of these proteins. In addition, we review the prognostic and clinical significance of these proteins in human cancers and, more importantly, the different approaches that have been used to disrupt PLK1 and FOX TF-mediated signaling networks. Furthermore, we discuss the therapeutic potential of targeting PLK1-regulated FOX TFs in human cancers.

Integrated bulk and single-cell RNA sequencing identifies an aneuploidy-based gene signature to predict sensitivity of lung adenocarcinoma to traditional chemotherapy drugs and patients’ prognosis

“…PLK1 is high-expressed in various cancers and is related to unfavorable prognosis ( Galusic et al, 2020 ). Increasing evidence suggested that PLK1 regulates several critical TFs in cancers and facilitates cell proliferation, metastasis, epithelial mesenchymal transition ( Moore, Gheghiani & Fu, 2023 ; Iliaki, Beyaert & Afonina, 2021 ). These findings indicated that PLK1 may be a promising target for cancer treatment.…”