부산대학교 도서관

The presynaptic cytomatrix protein Piccolo, encoded by PCLO, is frequently mutated and amplified in esophageal squamous cell carcinoma (ESCC), but its exact roles in ESCC remain unclear. Here we report that Piccolo expression correlates significantly with clinical stage, patient survival and tumor embolus. Functional studies demonstrate that PCLOknockdown remarkably attenuates ESCC malignancy in vitroand in vivo, and ectopic EGFR expression partially compensates for Piccolo loss. PCLOknockdown promotes ubiquitination and degradation of EGFR, which is associated with the negative regulatory effect of Piccolo on E3 ligase Siah1. An anti-Piccolo monoclonal antibody inhibited tumor proliferation in a mouse model of ESCC. These results demonstrate that Piccolo contributes to tumor aggressiveness in ESCC, likely by stabilizing EGFR and promoting EGFR-dependent signaling. Our results further suggest that Piccolo may represent a novel prognostic biomarker and therapeutic target for patients with ESCC.