Investigating the role of PTPRK in homeostasis and disease

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.

Name dc:type.qualificationname

Doctor of Philosophy (PhD)

Level dc:type.qualificationlevel

Doctoral

Grantor dc:publisher.institution

University of Cambridge

Year dc:date.issued

2022

Author dc:creator

• Young, Katherine

Advisor dc:contributor.advisor

• Sharpe, Hayley

• phosphatases

Licence

• https://www.repository.cam.ac.uk/bitstreams/5aba8824-d88c-4ee5-b297-ae52e0884532/download
• https://www.rioxx.net/licenses/all-rights-reserved/

Language dc:language

eng

DOI dc:identifier.doi

https://doi.org/10.17863/CAM.100006

OAI identifier oai:identifier

oai:www.repository.cam.ac.uk:1810/353989