A wake-up call to quiescent cancer cells: potential use of DYRK1B inhibitors in cancer therapy.

A wake-up call to quiescent cancer cells: potential use of DYRK1B inhibitors in cancer therapy.

FEBS J. 2017 Nov 28;:

Authors: Becker W

Abstract
Non-dividing cancer cells are relatively resistant to chemotherapeutic drugs and environmental stress factors. Promoting cell cycle re-entry of quiescent cancer cells is a potential strategy to enhance the cytotoxicity of agents that target cycling cells. It is therefore important to elucidate the mechanisms by which these cells are maintained in the quiescent state. The protein kinase DYRK1B is overexpressed in a subset of cancers and maintains cellular quiescence by counteracting G0 /G1 - S phase transition. Specifically, DYRK1B controls the S phase checkpoint by stabilizing the CDK inhibitor p27Kip1 and inducing the degradation of cyclin D. DYRK1B also stabilizes the DREAM complex that represses cell cycle gene expression in G0 arrested cells. In addition, DYRK1B enhances cell survival by upregulating antioxidant gene expression and reducing intracellular levels of reactive oxygen species (ROS). Substantial evidence indicates that depletion or inhibition of DYRK1B drives cell cycle re-entry and enhances apoptosis of those quiescent cancer cells with high expression of DYRK1B. Furthermore, small molecule DYRK1B inhibitors sensitize cells to the cytotoxic effects of anti-cancer drugs that target proliferating cells. These encouraging findings justify continued efforts to investigate the use of DYRK1B inhibitors to disrupt the quiescent state and overturn chemoresistance of non-cycling cancer cells. This article is protected by copyright. All rights reserved.

PMID: 29193696 [PubMed - as supplied by publisher]

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