A study of focal adhesion kinase in cancer using drosophila melanogaster

Macagno, Juan Pablo (2013) A study of focal adhesion kinase in cancer using drosophila melanogaster. PhD thesis, University of Glasgow.

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Abstract

Cancer is a group of diseases that affects almost every organ of the human body. A normal cell transforms into a cancer cell as a consequence of cumulative failures that alter diverse cellular processes such as cell proliferation, adhesion, migration, and cell death. Focal Adhesion Kinase (FAK) is a ubiquitous protein that is involved in all these cellular processes. Therefore, it is not surprising that FAK plays important roles in cancer; in fact, it has been linked to tumour progression or regression depending on the cellular and genetic context. We used Drosophila melanogaster as a model organism to study FAK’s duality in cancer. In this thesis we describe two novel roles of Drosophila FAK (FAK56): as a tumour suppressor within receptor tyrosine kinases (RTKs)-driven contexts, and as a tumour promoter by inhibiting cell death in nervous tissues. We investigated how FAK56 regulates signalling resulting from the overexpression of RTKs RET and EGFR. Our data indicated that FAK is a suppressor of RTKs in fly epithelia. This was also observed in human cancer cell lines, suggesting an evolutionary conserved mechanism. On the other hand, we found FAK56 prevented caspase-dependent cell death and uncovered a novel link between FAK56 and Relish, the Drosophila homologue of human NF-κB: Relish mutants suppressed FAK56 loss-induced cell death in the larval central nervous system and eye imaginal discs. As supported by the results presented in this thesis, FAK may be a good therapeutic target in cancer biology; however, in some contexts it may also behave as a tumour suppressor. Therefore, we conclude it will be necessary to identify the context of FAK activity before designing therapeutic strategies against FAK-expressing tumours.

Item Type: Thesis (PhD)
Qualification Level: Doctoral
Keywords: Drosophila, cancer, FAK, RTK, RET, EGFR, cell death
Subjects: Q Science > Q Science (General)
Colleges/Schools: College of Medical Veterinary and Life Sciences > Institute of Cancer Sciences > Beatson Institute of Cancer Research
Funder's Name: UNSPECIFIED
Supervisor's Name: Vidal, Dr. Marcos
Date of Award: 2013
Depositing User: Mr Juan Pablo Macagno
Unique ID: glathesis:2013-4863
Copyright: Copyright of this thesis is held by the author.
Date Deposited: 29 Jan 2014 12:28
Last Modified: 25 Jan 2017 10:27
URI: http://theses.gla.ac.uk/id/eprint/4863

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