G1 Dynamics at the Crossroads of Pluripotency and Cancer

SIMPLE SUMMARY: The cell division cycle is tightly regulated to ensure faithful and complete DNA replication. A critical cell cycle phase is G1 in which cells prepare DNA for replication in S phase. Interestingly, stem cells and cancer cells have both similarities and differences in their cell cycle regulatory mechanisms. In this review, we address the role of various cell cycle regulators in controlling the dynamics of G1 phase in stem cells and cancer cells. We also discuss recent advances in understanding how core pluripotency factors regulate the cell cycle and play dual roles in stem cell pluripotency and in cancers where they are aberrantly expressed. A better understanding of these common regulatory networks could offer potential new therapeutic avenues for cancer. ABSTRACT: G1 cell cycle phase dynamics are regulated by intricate networks involving cyclins, cyclin-dependent kinases (CDKs), and CDK inhibitors, which control G1 progression and ensure proper cell cycle transitions. Moreover, adequate origin licensing in G1 phase, the first committed step of DNA replication in the subsequent S phase, is essential to maintain genome integrity. In this review, we highlight the intriguing parallels and disparities in G1 dynamics between stem cells and cancer cells, focusing on their regulatory mechanisms and functional outcomes. Notably, SOX2, OCT4, KLF4, and the pluripotency reprogramming facilitator c-MYC, known for their role in establishing and maintaining stem cell pluripotency, are also aberrantly expressed in certain cancer cells. In this review, we discuss recent advances in understanding the regulatory role of these pluripotency factors in G1 dynamics in the context of stem cells and cancer cells, which may offer new insights into the interconnections between pluripotency and tumorigenesis.