F-Box protein 4 inhibits progression of papillary thyroid cancer

Abstract

Objective: We aimed to investigate the role of F-Box protein 4 (FBXO4) in the progression of papillary thyroid cancer (PTC) and to reveal the underlying signaling pathways responsible for FBXO4 action in PTC.

Methods: FBXO4 expression was evaluated in tissues from PTC patients as well as in cell lines. Overexpression of FBXO4 was re-introduced into PTC cell line B-CPAP, followed by analysis of cell migration, invasion, apoptosis and epithelial-mesenchymal transition (EMT) marker profile. An in vivo xenograft tumor mouse model was employed to address the role of FBXO4 in tumorigenesis as well.

Results: Endogenous FBXO4 was downregulated in PTC patient tissues and cell lines. Upon re-introducing its expression, FBXO4 suppressed migration and invasion and induced apoptosis of PTC cells, as well as inhibited EMT. Using a xenograft tumor mouse model, the pro-apoptotic and anti-EMT functions of FBXO4 are also validated in vivo, resulting in considerably slowed tumor growth rate of inoculated FBXO4-expressing PTC cells.

Conclusion: Our results therefore propose the potential therapeutic value of FBXO4 in targeted treatments against PTC.

Keywords: Apoptosis; Epithelial-mesenchymal transition; F-Box protein 4; Papillary thyroid cancer; Tumorigenesis.