Oncogenic Role and Clinical Significance of NPM1 in Colorectal Cancer via the AKT/mTOR Signaling Pathway

Background/Aim: Colorectal cancer (CRC) remains a major global health challenge with poor survival in advanced disease. Identifying new oncogenic drivers is essential for improving diagnosis and therapy. This study investigated the oncogenic role of nucleophosmin 1 (NPM1) in CRC and its involvement in the AKT/mTOR signaling pathway. Materials and Methods: TCGA-COAD datasets were analyzed to compare NPM1 expression in tumor and normal tissues. Functional assays (MTT proliferation, soft agar colony formation, migration, and in vivo xenograft models) were performed after siRNA-mediated NPM1 knockdown in HCT-116 and DLD-1 cells. Western blotting and phospho-kinase arrays were used to evaluate phosphorylation of AKT, mTOR, and p70 S6 kinase. Results: NPM1 expression was significantly upregulated in CRC tissues. Knockdown of NPM1 suppressed proliferation, migration, anchorage-independent growth, and in vivo tumorigenicity. Mechanistically, NPM1 depletion reduced phosphorylation of AKT, mTOR, and p70 S6 kinase, while total protein levels were unchanged. Downstream oncogenic regulators, including MYC and AP-1 components (c-Jun and c-FOS), were also decreased. Conclusion: NPM1 acts as an oncogenic driver in colorectal cancer by activating the AKT/mTOR signaling pathway. Elevated NPM1 expression highlights its potential as a diagnostic, prognostic, and therapeutic biomarker in CRC.