Prefoldin Subunit 2 Promotes Migration of Hepatocellular Carcinoma Cells and Is Associated with Poor Prognosis

Prefoldin subunit 2 (PFDN2), a component of the prefoldin complex, has been implicated in tumor progression and in cytoskeleton-related progression; however, its clinical relevance and biological role in hepatocellular carcinoma (HCC) remain unclear. This study investigated the clinicopathological relevance and functional role of PFDN2 in HCC.

Protein expression of prefoldin subunits (PFDN1-6) was examined in 265 HCC specimens using tissue microarrays. Associations with clinicopathological features and survival outcomes were analyzed. Functional roles of PFDN2 were assessed using Huh7 cells overexpressing PFDN2 (PFDN2-OE) and HLF cells with PFDN2 knockdown (PFDN2-KD). Migration, invasion, and proliferation assays were conducted, along with western blot analyses of Rac1-associated signaling and endoplasmic reticulum (ER) stress markers.

Elevated PFDN2 expression was significantly associated with poor tumor differentiation and vascular invasion. Patients with high PFDN2 expression had worse overall and recurrence-free survival (p = 0.0257 and p = 0.0255, respectively). In vitro, PFDN2-OE enhanced migratory capacity and lamellipodia formation, accompanied by upregulation of Rac1, phosphorylated Rac1, Tiam1, and ARHGAP1. PFDN2-KD suppressed proliferation and increased ER stress markers, including PERK, phosphorylated PERK, and CHOP.

PFDN2 overexpression is associated with aggressive tumor features and poor prognosis in HCC. PFDN2 promotes migratory activity through Rac1-associated signaling and may support cellular proliferation. These findings suggest that PFDN2 may serve as a molecular indicator of aggressive tumor behavior and potentially contribute to postoperative risk stratification.