PTPRK, a receptor tyrosine phosphatase, plays a crucial role in regulating cell-cell adhesion, growth factor signaling, and tumor suppression. It has both catalytic and non-catalytic functions that are important in understanding its impact on colorectal health and cancer development, providing new insights into its diverse functions.
Researchers at the Babraham Institute’s Sharpe lab explored the functions and signaling mechanisms of PTPRK in human cell adhesion, growth factor signaling, and tumor suppression in colon cells and colorectal cancer cells. Their findings, published in the Journal of Cell Science, enhance our understanding of the cellular processes that regulate tumor growth and repair after injury, shedding light on potential avenues for combating cancer metastasis.
Dr. Katie Young, the lead author of the study conducted during her time as a PhD student in the Sharpe lab, aimed to delve into PTPRK’s role in colon health, bridging various research findings to unravel the complex signaling pathways. Understanding how receptor protein tyrosine phosphatases like PTPRK transmit signals is crucial for maintaining cell health and preventing disease.
The research team observed that deleting PTPRK in human colorectal cancer cells impacted cell appearance and impaired wound-healing responses, indicating a disruption in cell coordination and polarization. In a mouse model lacking PTPRK, researchers noted a critical role for PTPRK in colon repair, where mice without PTPRK showed heightened susceptibility to colitis-induced inflammation and developed more aggressive colorectal tumors.
By utilizing a catalytic mutant with disabled enzymatic function and a xenograft model involving transplanted cancer cells, the team confirmed PTPRK’s role in tumor suppression, highlighting its independence from phosphatase activity. Furthermore, analyzing gene expression changes in cells lacking PTPRK revealed alterations in genes associated with epithelial cell identity and repair mechanisms.
Dr. Hayley Sharpe, the group leader of the Signaling research program at the Institute, emphasized the need to unravel PTPRK’s non-catalytic signaling functions, which play a pivotal role in suppressing tumor growth independent of its enzymatic activities. The team’s work suggests that PTPRK modulates epidermal growth factor receptor (EGFR) signaling as a key mechanism to suppress tumor development.
