Figure 1.

Roles of SPINK1. (A) In the pancreas, SPINK1 acts as an important regulator of protease activity. SPINK1 is co-expressed with trypsinogen by the pancreatic acinar cells and secreted from zymogen granules into the pancreatic duct. Within the acinar cells or the duct, SPINK1 quenches prematurely activated trypsin to prevent further protease activation and organ damage. (B) Tumor cell secreted SPINK1 inhibits unknown serine protease(s) to induce anoikis resistance, tumor cell survival and metastatic disease. (C) Tumor cell secreted SPINK1 activates EGFR kinase pathways and leads to tumor cell proliferation; the direct receptor of SPINK1 in this context requires further definition. (D) Sequence alignment using Clustal Omega comparing human, mouse, and rat EGF with human, mouse, and rat SPINK1 (ISK1) homologs. Identified are sequence identity between hEGF and hSPINK1, sequence identities across all three species, and disulfide bond pattern.