Oncogenic Role and Clinical Significance of NPM1 in Colorectal Cancer 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 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 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.