Biology subjects

Chusorn, P.

Publications and source records attributed to Chusorn, P..

2 recordsLinked to original sources

bioRxiv2024

Exploring the Single-Cell Dynamics of FOXM1 Under Cell Cycle Perturbations

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.

systems biology↗

bioRxiv2023

Chemically Tunable FOXM1-D Sensor Revealed FOXM1 Direct Influence on Cell Cycle

Forkhead box protein M1 (FOXM1) is a proliferation-associated transcription factor contributing to the G2/M phase transition of the cell cycle. Although the upregulation of FOXM1 has been observed in different cancer types, how the regulation of FOXM1 dynamically alters during cell cycles and potentially contributes to tumorigenesis is not well understood. We showed here the development and application of a tunable FOXM1-DHFR (FOXM1-D) sensor that enables surveillance and manipulation of the FOXM1 abundance. Using trimethoprim (TMP) to stabilize the sensor, we measured the kinetics of FOXM1-D production, degradation, and cytosolic-to-nuclear translocation in the G1 and G2 cell-cycle phases. By controlling FOXM1-D stability in different synchronized cell cycle pools, we found that the G1- and S-synchronized cells finished their first cell division faster, although the G2-synchronized cells were unaffected. Our analysis of single-cell FOXM1-D dynamics revealed that the two-round dividing cells had a lower amplitude and later peak time than those arrested in the first cell division. Destabilizing FOXM1-D in the single-round dividing cells enabled these cells to re-enter the second cell division, proving that overproduction of FOXM1 causes cell cycle arrest and prevents unscheduled proliferation.

cell biology↗