POM121 Drives Gastric Cancer Progression via the mTOR/p70S6K Signaling Axis

Background/Aim: Gastric cancer (GC) remains one of the leading causes of cancer-related mortality worldwide. This study aimed to clarify the oncogenic function of POM121 and its involvement in signaling pathways driving tumor progression. Materials and Methods: POM121 expression was analyzed in six GC cell lines and one normal gastric epithelial cell line, as well as in clinical datasets. Functional consequences of POM121 knockdown were assessed in AGS and KATO-III cells using cell proliferation, migration, soft agar colony formation, proteomic profiling, and in vivo xenograft models. Phosphorylation of p70S6 kinase at Thr389 and Thr421/Ser424 was examined to determine downstream signaling. Results: POM121 was consistently found to be upregulated in GC tissues and cell lines. Silencing of POM121 significantly inhibited proliferation, migration, anchorage-independent growth, and tumorigenicity in vivo. Proteomic analysis revealed that suppression of POM121 attenuated phosphorylation of p70S6K at Thr389 and Thr421/Ser424, indicating impaired mTOR-p70S6K signaling. Conclusion: POM121 promotes GC progression by enhancing proliferative and invasive phenotypes through p70S6 kinase-mediated signaling. These findings establish POM121 as a novel oncogene, prognostic biomarker, and potential therapeutic target in GC.