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 differentially triggers the proliferation propensities in CSCs in an origin-dependent manner by controlling the expression of the key transcription factor like Nanog. However, the factors that critically govern this glucose-stimulated proliferation dynamics of CSCs remains elusive. Herein, by proposing a mathematical model of glucose-mediated Nanog regulation in CSCs, we showed that the differential proliferation behavior of 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 specific CSCs in a context-dependent manner. In future, these modeling insights will be useful in developing improved therapeutic strategies to get rid of harmful CSCs.