Figure 1. Proposed model for ETV4 (E26 transformation-specific (ETS) variant 4) overexpression that is involved in the pathobiology of pancreatic cancer.

ETV4 overexpression can be mediated by multiple signaling events including activation of K-Ras. Binding of a ligand specific to EGFR and MET receptors leads to activation of K-Ras which activates RAF, mitogen-activated protein kinase (MEK) and extracellular signal-regulated kinase (ERK) signaling pathways. These signaling events subsequently activate transcription factor ETV4. The activated ETV4 upregulates the expression of cyclin D1 and MMPs (matrix metalloproteinase) leading to tumor growth, invasion, and metastasis. Gray arrow indicates that the connection of signaling molecules with ETV4 recognized in other malignancies, however, it is still unexplored in pancreatic cancer.