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ABSTRACT The cell cycle is crucial for maintaining normal cellular functions and preventing replication errors. FOXM1, a key transcription factor, plays a pivotal role in regulating cell cycle progression and is implicated in various physiological and pathological processes, including cancers like liver, prostate, breast, lung, and colon cancer. Despite previous research, our understanding of FOXM1 dynamics under different cell cycle perturbations and its connection to heterogeneous cell fate decisions remains limited. In this study, we investigated FOXM1 behavior in individual cells exposed to various perturbagens. We found that different drugs induce diverse responses due to heterogeneous FOXM1 dynamics at the single-cell level. Single-cell analysis identified six distinct cellular phenotypes: on-time cytokinesis, cytokinesis delay, cell cycle delay, G1 arrest, G2 arrest, and cell death, observed across different drug types and doses. Specifically, treatments with PLK1, CDK1, CDK1/2, and Aurora kinase inhibitors revealed varied FOXM1 dynamics leading to heterogeneous cellular outcomes. Our findings affirm that FOXM1 dynamics are pivotal in determining cellular outcomes, independent of the specific inhibitor employed. Our results gave insights into how FOXM1 dynamics contribute to cell cycle fate decisions, especially under different cell-cycle perturbations.
Jawwad et al. (Sun,) studied this question.