INSR and familial pancreatic carcinoma: To interrogate the effect of heparanase overexpression on insulin-INSR pathway in the setting of pancreatic cancer, we first applied PANC1 cells (human PDAC cell line expressing low levels of endogenous heparanase, Supplementary Figure S1) stably transfected with a vector encoding for human heparanase (PANC1-hpse) or control empty vector (PANC1-Vo).