Unraveling the origin of glucose mediated disparate proliferation dynamics of cancer stem cells

Cancer stem cells (CSCs) often switch on their self-renewal programming aggressively to cause a relapse of cancer. Intriguingly, glucose triggers the proliferation propensities in CSCs by controlling the expression of the key transcription factor-like Nanog. However, the factors that critically govern this glucose-stimulated proliferation dynamics of CSCs remain elusive. Herein, by proposing a mathematical model of glucose-mediated Nanog regulation, we showed that the differential proliferation behavior of CSCs and cell-type similar to CSCs can be explained by considering the experimentally observed varied expression levels of key positive (STAT3) and negative (p53) regulators of Nanog. Our model reconciles various experimental observations and predicts ways to fine-tune the proliferation dynamics of these cell types in a context-dependent manner. In future, these modeling insights will be useful in developing improved therapeutic strategies to get rid of harmful CSCs. (C) 2021 Elsevier Ltd. All rights reserved.