Our findings that silencing of SDC-2 not only reduces Src Tyr416 phosphorylation and ras activity, but also (downstream) ERK phosphorylation, might be interpreted in two ways: firstly, Su8686 pancreatic cancer cells are K-ras-independent and syndecan-2 RNAi signals to K-ras as well as directly into the MAPK pathway or secondly, Su8686 cells are K-ras-dependent and ablation of the (intact) K-ras signal effects its downstream targets and thus reduces invasiveness and migration. Here, SDC2 is linked to familial pancreatic carcinoma.