PFND1 Predicts Poor Prognosis of Gastric Cancer and Promotes Cell Metastasis by Activating the Wnt/β-Catenin Pathway.

Abstract

BackgroundPrefoldin (PFDN) subunits have recently been found to function importantly in various tumor types, while the role of PFDN subunit 1 (PFDN1) in gastric cancer (GC) remains largely unknown. Herein, we aimed to investigate the clinical significance, the biological role and the underlying mechanism of PFDN1 in GC development.Materials and MethodsPFDN1 expression levels were measured in human GC specimens by quantitative real-time PCR (qRT-PCR), Western blot and immunohistochemistry. Furthermore, the effects of aberrant PFDN1 expression on GC cells behavior were assessed by wound-healing assay and transwell assay in vitro, and metastasis assay in nude mice, as well as Wnt/β-catenin signaling-induced epithelial–mesenchymal transition (EMT)-related markers by qRT-PCR and Western blot.ResultsPFDN1 levels were significantly upregulated in GC tissues compared with those in matched adjacent normal tissues. PFDN1 upregulation correlated strongly with clinical metastasis and unfavorable prognosis for GC patients. In vitro and in vivo studies revealed that PFDN1 facilitated GC cell migration, invasion and metastasis. Mechanically, PFDN1 modulated GC cell behavior by activating Wnt/β-catenin signaling-mediated EMT.ConclusionThese results suggested a central role of PFDN1 in GC metastatic development via the Wnt/β-catenin pathway, thus providing a potential therapeutic target for patients with GC.