Characterization of The Expression of The Heavy Chain of 4F2 Antigen As a Therapeutic Target in Prostate Cancer

Abstract

The 4F2 cell-surface antigen heavy chain (4F2hc) forms a heterodimeric complex with L-type amino acid transporter 1 (LAT1) and transports large neutral essential amino acids. However, in contrast to the traditional role of LAT1 in various cancers, the role of 4F2hc has largely remained unknown. The role of 4F2hc in prostate cancer was studied. Treatment of C4-2 cells with si4F2hc was found suppress cellular growth and migratory and invasive abilities, with this effect occurring through the cell cycle, with a significant decrease in S phase and a significant increase in G0/G1 phase, suggesting cell cycle arrest. In addition, it was proven by RNA seq that the key to 4F2hc’s impact on cancer is SKP2. The expression of 4F2hc and LAT1 in prostate cancer cells suggests the importance of 4F2hc. Furthermore, si4F2hc, through the downstream target SKP2, upregulates the protein expression of cyclin-dependent kinase inhibitors (P21cip1, P27kip1). Multivariate analysis showed that high 4F2hc expression was an independent prognostic factor for progression-free survival (HR 11.54, p=0.0357). High 4F2hc was related to the clinical tumour stage (p=0.0255) and Gleason score (p=0.0035). Collectively, 4F2hc contributed significantly to prostate cancer (PC) progression. 4F2hc may be a novel marker and therapeutic target in PC.