PRKD1/EIF5A/β-catenin axis inhibits tumorigenesis and metastasis in non-small-cell lung cancer.

PRKD1 is downregulated in non-small-cell lung cancer (NSCLC). Whether and how PRKD1 regulates tumorigenesis and metastasis is previously unknown. Here, we report that PRKD1 negatively regulates β-catenin protein abundance. PRKD1 promotes ubiquitination and degradation of EIF5A. EIF5A upregulates β-catenin and activates the Wnt signaling pathway. Thus, the PRKD1/EIF5A/β-catenin axis modulates the Wnt signaling pathway in NSCLC. Functionally, PRKD1 inhibits cell proliferation and metastasis both in vitro and in vivo. PRKD1 is downregulated and EIF5A is upregulated in NSCLC. Lower PRKD1 and higher EIF5A predict a worse patient survival. Our study suggests that the PRKD1/EIF5A/β-catenin axis is involved in the carcinogenesis of NSCLC and may serve as a new therapeutic target for NSCLC. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s10238-026-02068-9.