PF4V1 affects the progression of oral squamous cell carcinoma by regulating Wnt/β-catenin pathway and angiogenesis

Abstract

Platelet factor-4 variant 1 (PF4V1) was recently described as a natural non-allelic gene variant of platelet factor-4 (PF4), which has been closely associated with the growth and metastasis of various cancers. Our previous research showed that PF4V1 was related to oral squamous cells carcinoma (OSCC) metastasis. Howerver, it is still not clear about the functional role of PF4V1 in OSCC. In this study, stably transfected cell lines were constructed and the expression level of PF4V1 was verified by real-time polymerase chain reaction (RT-PCR) and western blot. The effect of PF4V1 on proliferation, migration, invasion, and apoptosis of oral cancer (OC) cells were detected. Moreover, a xenograft tumor model was constructed to evaluate the effect of PF4V1 on OSCC in vivo. Indicators of Wnt/β-catenin, angiogenesis and epithelial-mesenchymal transition (EMT) pathways were also examined. Stable cell lines with overexpression and inhibited expression of PF4V1 were constructed successfully. After stable transfection, PF4V1 significantly promoted the proliferation, migration, and invasion of OC cells in vitro, and their tumor formation in vivo. Furthermore, PF4V1 remarkably promoted the expression of β-catenin, VEGF, and FGF but suppressed the expression of GSK-3β. There was no statistically significant correlation between PF4V1 and EMT pathway. This study provides evidence that PF4V1 promotes the proliferation, migration, invasion and tumor formation of OC cells by regulating the Wnt/β-catenin pathway and angiogenesis. Our findings suggest that PF4V1 could be a very promising target of OSCC therapy in the future.

A Label-Free Proteomic Approach for the Identification of Biomarkers in the Exosome of Endometrial Cancer Serum

“…PF4V1 suppresses chemokine angiogenesis by blocking the protein bFGF, and is closely associated with the growth and metastasis of various cancers [ 35 ]. It is known that PF4V1 in prostate cancer leads to suppression of proliferation and invasion, and serves as a potential prognostic biomarker [ 36 ].…”

Rapamycin as a potent and selective inhibitor of vascular endothelial growth factor receptor in breast carcinoma

“…11 According to the literature, three different mechanisms have been proposed to explain the inhibitory effects of PF-4 on the angiogenesis process. 12 The first mechanism, PF-4, may bind to proteoglycans and interfere with the proteoglycan-bystander impact on growth factor activity. The second mechanism is that PF-4 molecules can interact directly with angiogenesis growth factors such as fibroblast growth factors or vascular endothelial growth factors and inhibits the interaction of growth factors with cell surface receptors.…”