FAM111B promotes prostate cancer progression by inhibiting apoptosis via ATF3 suppression and MAPK pathway activation: a novel biomarker and therapeutic target.

[BACKGROUND] Prostate cancer (PCa) ranks among the most prevalent and aggressive malignancies in men worldwide, with its incidence continuing to rise. This study investigates the role of FAM111B in PCa progression and evaluates its potential as both a biomarker and a therapeutic target.

[METHODS] We assessed FAM111B expression and function using in vitro and in vivo PCa models. Quantitative PCR, Western blotting, and immunofluorescence assays were employed to determine FAM111B’s effects on apoptosis and on the MAPK signaling cascade. Rescue experiments were performed to elucidate ATF3’s involvement in mediating FAM111B-driven changes in PCa progression.

[RESULTS] FAM111B levels were significantly elevated in PCa cell lines and patient-derived tumor tissues. Mechanistically, FAM111B downregulated ATF3, thereby diminishing ATF3’s occupancy at the KRAS promoter. This reduction led to upregulated KRAS expression and enhanced activation of the RAF1–MEK–ERK pathway, which in turn inhibited apoptosis and promoted PCa cell survival. Conversely, FAM111B knockdown increased apoptotic markers, while its overexpression activated MAPK signaling and suppressed pro‑apoptotic factors.

[CONCLUSIONS] Our findings demonstrate that FAM111B drives PCa progression by repressing ATF3 and activating the MAPK pathway to inhibit apoptosis. These results position FAM111B as a promising biomarker and a potential therapeutic target, especially in castration‑resistant prostate cancer (CRPC).

[SUPPLEMENTARY INFORMATION] The online version contains supplementary material available at 10.1186/s12935-025-04111-3.