Imperial College London
Alternate

ProfessorLucaMagnani

Faculty of Medicine, Department of Surgery & Cancer

Honorary Principal Research Fellow
 
 
 
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Contact

 

+44 (0)20 7594 2808l.magnani CV

 
 
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Location

 

137ICTEM buildingHammersmith Campus

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Summary

 

Publications

Citation

BibTex format

@article{Varghese:2019:10.1038/s41598-018-38017-0,
author = {Varghese, V and Magnani, L and Harada, N and Mauri, F and Szydlo, R and Yao, S and Lam, E and Kenny, L},
doi = {10.1038/s41598-018-38017-0},
journal = {Scientific Reports},
title = {FOXM1 modulates 5-FU resistance in colorectal cancer through regulating TYMS expression},
url = {http://dx.doi.org/10.1038/s41598-018-38017-0},
volume = {9},
year = {2019}
}
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RIS format (EndNote, RefMan)

TY  - JOUR
AB  - Resistance to 5-Fluoruracil (5-FU) has been linked to elevated expression of the main target, thymidylate synthase (TYMS), which catalyses the de novo pathway for production of deoxythymidine monophosphate. The potent oncogenic forkhead box transcription factor, FOXM1 is is regulated by E2F1 which also controls TYMS. This study reveals a significant role of FOXM1 in 5-FU resistance. Overexpression and knock-down studies of FOXM1 in colon cancer cells suggest the importance of FOXM1 in TYMS regulation. ChIP and global ChIP-seq data also confirms that FOXM1 can also potentially regulate other 5-FU targets, such as TYMS, thymidine kinase 1 (TK-1) and thymidine phosphorylase (TYMP). In human colorectal cancer tissue specimens, a strong correlation of FOXM1 and TYMS staining was observed. Elevated FOXM1 and TYMS expression was also observed in acquired 5-FU resistant colon cancer cells (HCT116 5-FU Res). A synergistic effect was observed following treatment of CRC cells with an inhibitor of FOXM1, thiostrepton, in combination with 5-FU. The combination treatment decreased colony formation and migration, and induced cell cycle arrest, DNA damage, and apoptosis in CRC cell lines. In summary, this research demonstrated that FOXM1 plays a pivotal role in 5-FU resistance at least partially through the regulation of TYMS.
AU  - Varghese,V
AU  - Magnani,L
AU  - Harada,N
AU  - Mauri,F
AU  - Szydlo,R
AU  - Yao,S
AU  - Lam,E
AU  - Kenny,L
DO  - 10.1038/s41598-018-38017-0
PY  - 2019///
SN  - 2045-2322
TI  - FOXM1 modulates 5-FU resistance in colorectal cancer through regulating TYMS expression
T2  - Scientific Reports
UR  - http://dx.doi.org/10.1038/s41598-018-38017-0
UR  - http://hdl.handle.net/10044/1/65300
VL  - 9
ER  -
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