Protease-activated receptor 2 drives migration in a colon cancer cell line but not in non-cancerous human epithelial cells

Am J Physiol Gastrointest Liver Physiol. 2024 Mar 5. doi: 10.1152/ajpgi.00284.2023. Online ahead of print.ABSTRACTThe inflamed mucosa contains a complex assortment of proteases which may participate in wound healing or in the development of inflammation-associated colon cancer. We sought to determine the role of protease-activated receptor 2 (PAR2) in epithelial wound healing in both untransformed and transformed colonic epithelial cells. Monolayers of primary epithelial cells derived from organoids cultivated from patient colonic biopsies, and of the T84 colon cancer cell line, were grown to confluence, wounded in the presence of a selective PAR2-activating peptide, and healing visualized by live cell microscopy. Inhibitors of various signaling molecules were used to assess the relevant pathways responsible for wound healing. Activation of PAR2 induced an enhanced wound healing response in T84 but not primary cells. The PAR2-enhanced wound healing response was associated with the development of lamellipodia in cells at the wound edge, consistent with sheet migration. The response to PAR2 activation in T84 cells was completely dependent upon Src kinase activity, and partially dependent on Rac1 activity. The Src-associated signaling molecules, focal adhesion kinase and epidermal growth factor receptor, which typically mediate wound healing responses, were not involved in the PAR2 response. Experiments repeated in the presence of the inflammatory cytokines, TNF and IFNγ, revea...
Source: Am J Physiol Gastroi... - Category: Gastroenterology Authors: Source Type: research