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Investigating the role of PTPRK in homeostasis and disease https://doi.org/10.17863/CAM.100006 Young, Katherine Sharpe, Hayley Cell communication is critical in orchestrating a proportionate response to external factors, such as growth factors and during essential processes, such as junctional remodelling. Plasma membrane-localised receptor PTPs (RPTP) are well positioned to sense external environmental cues, such as cell-cell contact, and transmit signals via their intracellular domains. Using unbiased approaches we find RPTP, PTPRK binds and dephosphorylates key junctional regulators in epithelial cells. Consequently, PTPRK knockout (KO) epithelial cells exhibit impaired morphology and junctional integrity. In parallel, we find *Ptprk* KO mice are more susceptible to DSS-induced colitis and exhibit increased growth and invasion in a colorectal cancer model. These observations support its putative role as a tumour suppressor in several cancer types and its association with inflammatory bowel disease. Strikingly, we find that the ability of PTPRK to supress tumour growth in a colorectal cancer xenograft model does not require its catalytic activity. We employ the use of multi-omics to discover that this phenotype could be attributed to an enhanced susceptibility to growth factor stimulation, particularly epidermal growth factor. University of Cambridge 2022-12-01 Thesis Doctoral Doctor of Philosophy (PhD) eng https://www.repository.cam.ac.uk/handle/1810/353989 https://www.repository.cam.ac.uk/bitstreams/e80bf34e-9a1e-4ce5-a3ee-0572d16e1551/download 08c25461611a625361159121af71fcc3 https://www.repository.cam.ac.uk/bitstreams/5aba8824-d88c-4ee5-b297-ae52e0884532/download 87eda9de84448d1f82354d60eee3eb5f https://www.rioxx.net/licenses/all-rights-reserved/ phosphatases