Use this URL to cite or link to this record in EThOS: http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.702763
Title: The regulation of FOXM1 in breast cancer
Author: Kongsema, Mesayamas
ISNI:       0000 0004 6059 1164
Awarding Body: Imperial College London
Current Institution: Imperial College London
Date of Award: 2014
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Abstract:
Breast cancer is the most commonly diagnosed cancer in women worldwide. In the UK, there is 1 in 8 of women that have a risk of being diagnosed with breast cancer in a lifetime. Clinically, the common treatment using for breast cancer therapy are combinations of surgery, radiotherapy, endocrinal (hormonal) therapy and chemotherapy. The DNA damaging agent epirubicin has been shown to be an effective chemotherapeutic drug for breast cancer treatment. Nevertheless, there are more than 90% of patients with metastatic cancer that found to be resistant to the drug. FOXM1 is a transcription factor that has been reported to be responsible for a resistance to various chemotherapeutics, including epirubicin. Accumulating evidence has revealed that FOXM1 is regulated by modifications at the post-translational levels. In this study, I show that FOXM1 can also be regulated by SUMOylation and ubiquitination. In response to epirubicin treatment, FOXM1 is modified primarily by SUMO1, and not SUMO2/3, in breast cancer cells. The SUMOylation of FOXM1 is targeted by RNF168 and leads to its ubiquitination, nuclear exportation and degradation through the proteasome degradation pathway. Unfortunately, the study about OTUB1 about its property in deubiquitinating ubiquitinated FOXM1 does not show the significant results. Collectively, this thesis identifies and characterises the role of SUMOylation, ubiquitination and RNF168 in modulating FOXM1 expression and activity, by promoting its degradation. My data suggest that these proteins and PTMs might be interesting targets for the development of novel therapeutic strategies for breast cancer treatment and for overcoming conventional chemotherapeutic drug resistance.
Supervisor: Lam, Eric Sponsor: Government of Thailand
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID: uk.bl.ethos.702763  DOI: Not available
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