A chemically tunable FOXM1-DHFR sensor reveals the direct influence of FOXM1 on the cell cycle
11
Issued Date
2025-07-15
Resource Type
eISSN
14779137
Scopus ID
2-s2.0-105012779806
Pubmed ID
40586720
Journal Title
Journal of Cell Science
Volume
138
Issue
14
Rights Holder(s)
SCOPUS
Bibliographic Citation
Journal of Cell Science Vol.138 No.14 (2025)
Suggested Citation
Phongkitkarun K., Chusorn P., Kamkaew M., Jamnongsong S., Lam E.W.F., Promptmas C., Sampattavanich S. A chemically tunable FOXM1-DHFR sensor reveals the direct influence of FOXM1 on the cell cycle. Journal of Cell Science Vol.138 No.14 (2025). doi:10.1242/jcs.263749 Retrieved from: https://repository.li.mahidol.ac.th/handle/123456789/111663
Title
A chemically tunable FOXM1-DHFR sensor reveals the direct influence of FOXM1 on the cell cycle
Author's Affiliation
Corresponding Author(s)
Other Contributor(s)
Abstract
Forkhead box protein M1 (FOXM1) is a transcription factor that is required for the G2/M transition and is frequently upregulated in cancers, promoting tumor progression and therapy resistance. However, its dynamic regulation throughout the cell cycle remains unclear. We developed a tunable FOXM1-dihydrofolate reductase (DHFR) sensor, FOXM1-D, in non-malignant MCF10A cells, enabling real-time monitoring and manipulation of FOXM1 levels. Using trimethoprim to stabilize FOXM1-D, we quantified its production, degradation and nuclear translocation during G1 and G2 phases. Overexpression of FOXM1-D accelerated cell division in G1 and S phases but did not affect G2-synchronized cells. Notably, 70-90% of FOXM1-D-overexpressing cells were arrested after the first division, whereas those with timely degradation could undergo a second division. Sustained FOXM1-D overexpression induced cell cycle arrest in daughter cells, highlighting the role of FOXM1 kinetics in determining cell fate. Sustained FOXM1-D upregulates p21 (also known as CDKN1A), triggering G1 arrest. Thus, targeting FOXM1 exploits its dual capacity to induce oncogene-induced senescence or suppress mitotic entry. Our study provides a basis for precision therapies that align interventions with FOXM1 kinetics to improve outcomes in FOXM1-driven tumors.