Evaluation of focal adhesion kinase as a novel radiosensitising target

Graham, Kathryn (2010) Evaluation of focal adhesion kinase as a novel radiosensitising target. PhD thesis, University of Glasgow.

Abstract

Focal adhesion kinase (FAK) is a cytoplasmic tyrosine kinase that is upregulated in a variety of human cancers. While there is evidence that FAK is implicated in a wide range of crucial cellular processes that are perturbed in malignancy including proliferation, cell cycle, adhesion and invasion, there is limited information regarding the role of FAK in radiation survival. We aimed to evaluate whether FAK is a novel radiosensitising target by studying clonogenicity in wt p53 FAK +/+ versus FAK -/- squamous cell carcinoma (SCC) cell lines generated in this laboratory. Surprisingly, the absence of FAK was associated with increased radioresistance. In this particular context, FAK indirectly inhibits p53 mediated transcriptional regulation of p21 in response to ionising radiation. Why FAK should repress the pro-survival function of p53 is unclear, but this data indicates that inhibition of FAK in combination with radiation may not always be advantageous in the clinical setting and contributes to an increasing body of literature highlighting a close interaction between FAK and p53.

• Item Type: Thesis (PhD)
• Qualification Level: Doctoral
• Keywords: radiotherapy, radiobiology, radiosensitivity, cancer, p53, FAK, novel targets
• Subjects: R Medicine > RC Internal medicine > RC0254 Neoplasms. Tumors. Oncology (including Cancer); Q Science > Q Science (General)
• Colleges/Schools: College of Medical Veterinary and Life Sciences > School of Cancer Sciences
• Supervisor's Name: Frame, Professor Margaret
• Date of Award: 2010
• Depositing User: Dr Kathryn Graham
• Unique ID: glathesis:2010-2181
• Copyright: Copyright of this thesis is held by the author.
• Date Deposited: 16 Nov 2010
• Last Modified: 10 Dec 2012 13:52
• URI: https://theses.gla.ac.uk/id/eprint/2181