Profilin 2 Promotes Proliferation and Metastasis of Head and Neck Cancer Cells by Regulating PI3K/AKT/β-Catenin Signaling Pathway.

Abstract

Profilin 2 (PFN2) was found to be mainly expressed in neurons and involved in the development of the brain. In recent years, emerging evidence indicated that PFN2 is also significantly upregulated in various cancers including head and neck cancer (HNSC) and influences cancer cell proliferation, migration, and invasion. However, the role of PFN2 in HNSC development and progression remains unclear. The aim of our study was to investigate the role of PFN2 in the development of HNSC and its possible molecular mechanisms. Bioinformatics showed that increased expression of PFN2 in tumors correlated highly with poor prognosis of HNSC patients. Our results indicated that PFN2 was highly expressed in HNSC tissues and in HNSC cell lines. Knockdown of PFN2 inhibited proliferation, invasion, and migration of HNSC cells, while PFN2 overexpression produced the opposite effects. Using a nude mouse xenograft model, we substantiated the tumor-promoting effect of PFN2 on HNSC in vivo. Furthermore, we found that PFN2 downregulation reduced the phosphorylation of Akt and GSK-3β and reduced the expression of β-catenin in HNSC cells. The opposite was observed when PFN2 was overexpressed. Collectively, these results suggest that PFN2 promotes the proliferation and metastasis of HNSC by activating the PI3K/Akt/β-catenin signaling pathway. Although further validation is needed, we speculate that PFN2 plays a crucial role in HNSC and may be a promising therapeutic target and prognostic biomarker.

• Authors: Kecheng Zhou, Jie Chen, Jiayu Wu, Yangxinzi Xu, Qiaoyun Wu, Jingjing Yue, Yu Song, Shengcun Li, Peng Zhou, Wenzhan Tu, Guanhu Yang, Songhe Jiang
• Journal: Oncology research (Oncol Res) Vol. 27 Issue 9 Pg. 1079-1088 (Sep 23 2019) ISSN: 1555-3906 [Electronic] United States
• PMID: 31122311 (Publication Type: Journal Article)

Chemical References

• CTNNB1 protein, human
• PFN2 protein, human
• Profilins
• beta Catenin
• Proto-Oncogene Proteins c-akt

Topics

• Animals
• Apoptosis (physiology)
• Cell Line, Tumor
• Cell Movement (physiology)
• Cell Proliferation (physiology)
• Head and Neck Neoplasms (genetics, metabolism, pathology)
• Heterografts
• Humans
• Mice
• Neoplasm Metastasis
• Phosphatidylinositol 3-Kinases (metabolism)
• Profilins (biosynthesis, genetics, metabolism)
• Proto-Oncogene Proteins c-akt (metabolism)
• Signal Transduction
• Up-Regulation
• beta Catenin (metabolism)