The protein tyrosine kinase 7 (PTK7): A novel player in the crosstalk between colonic epithelium and fibroblasts

ATTENTION : Séminaire au Pavillon 4 du bâtiment de la Surélévation (Campus des Cordeliers)

Expression of the protein tyrosine kinase 7 (PTK7) receptor in tumoral epithelium has been associated with poor prognosis in colorectal cancer (CRC). Interestingly, an antibody-drug conjugate targeting PTK7 triggers tumor regression in ovarian, lung and breast cancer xenografts and has entered phase 2 clinical trials. We set out to better understand the role of PTK7 in CRC.  In murine colon, we detected PTK7 expression in epithelial stem cells, as described in the literature. However, we also detected PTK7 expression in fibroblasts, which has been so far overlooked. Biopsies from CRC patients displayed distinct expression profiles for PTK7 in the epithelium and fibroblasts, suggesting a complex role for PTK7 in CRC.To explore the potential role of PTK7 in regulating the crosstalk between colonic epithelium and neighboring fibroblasts, we have generated cell type specific knock-out mice, by deleting Ptk7 in colonic epithelial cells upon tamoxifen injection(Ptk7fl/flVilCreERT2 mice) and a subpopulation of colonic fibroblasts (Ptk7fl/flColVICre mice), respectively. We started to analyze these mouse strains in homeostasis and colonic pathologies and I will present the results of these analyses. The data we obtained so far, suggest a disease suppressing role for a subset of PTK7 expressing colonic fibroblasts. Together, our findings suggest that PTK7 executes distinct roles in colon homeostasis and pathology.