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Focal adhesion kinase (FAK) is a non-receptor tyrosine kinase, commonly overexpressed in cancer that is well known to be a key regulator of cancer cell proliferation, survival, migration and invasion. It has recently been shown to modulate the antitumour immune response via transcriptional regulation of chemokines and cytokines. These findings have fuelled interest in FAK as a plausible therapeutic target in cancer and FAK kinase inhibitors are currently in Phase I and II clinical trials. To date, much of the research on FAK has focused on its role at focal adhesions, detailing its major functions in cell motility and cancer cell invasion. However, 16 years ago, FAK was shown to translocate to the nucleus and it is now well established that this occurs under conditions of cellular stress such as oncogenic transformation. In the nucleus, FAK binds to a number of transcription factors such as P53, MDM2, IL33, RUNX1 and SP1. These nuclear interactions have been linked to proliferation, survival, differentiation and regulation of the anti-tumour immune response and cell cycle. However, despite these findings, the mechanism by which FAK regulates gene expression in the nucleus has yet to be defined. With FAK kinase inhibitors currently in clinical trials, it is important to understand the molecular mechanisms associated with FAK’s transcriptional regulation, the role of the kinase activity, and the potential therapeutic benefits of targeting FAK’s nuclear function. We therefore investigated the mechanism by which FAK regulates transcription by integration of a number of ‘omics’ approaches to define the nuclear FAK interactome and FAK-dependent gene programmes, as well as FAK’s role in regulating chromatin accessibility and transcription factor binding. Integration of these datasets predicted that FAK regulates the binding of AP-1 and ETS transcription factors to chromatin. Furthermore, our findings indicate that a subset of FAK-regulated genes display changes in chromatin accessibility. Chromatin ImmunoPrecipitation (ChIP) validation experiments on the enhancer region of one of these genes, IL33, show reduced binding of JUN upon loss of FAK’s kinase activity. This predicts that FAK is regulating chromatin accessibility at this region of the IL33 gene. The work presented in this thesis therefore identifies a novel mechanism by which FAK regulates transcription; further experiments will be required to define the epigenetic complexes responsible for FAK-dependent chromatin accessibility changes. This work adds to our understanding of how an integrin adhesion protein can control cancer cell behaviour via transcription in the nucleus.