AURKA phosphorylation licenses TRIM28-dependent SUMOylation to stabilize SPICE1 in prostate cancer bone metastasis

Bone metastasis is a major cause of disease progression and cancer-related death in advanced prostate cancer (PC). Although spindle and centriole associated protein 1 (SPICE1) has been implicated in tumor biology, its role in PC metastasis and its post-translational regulation remain largely unknown. SPICE1 expression was assessed in PC tissues and bone metastatic lesions, and its clinicopathological relevance was analyzed. functional assays were performed in PC3 and C42B cells to evaluate cell proliferation, migration, invasion, and epithelial–mesenchymal transition (EMT). Subcutaneous xenograft and intra-arterial bone metastasis models were used to determine the in vivo effects of SPICE1 silencing. Co-immunoprecipitation, proximity ligation assay, mutagenesis, cycloheximide chase, and ubiquitination/SUMOylation assays were employed to define the underlying mechanism. SPICE1 was markedly upregulated in PC tissues and was further increased in bone metastatic lesions. High SPICE1 expression was associated with aggressive clinicopathological features and poor prognosis. Functionally, SPICE1 knockdown suppressed PC cell proliferation, migration, invasion, and EMT in vitro, and attenuated tumor growth and bone metastasis in vivo. Mechanistically, AURKA directly interacted with SPICE1 and phosphorylated SPICE1 at serine 811, thereby enhancing SPICE1 stability. This phosphorylation event promoted the recruitment of the SUMO E3 ligase TRIM28 and facilitated TRIM28-dependent SUMOylation of SPICE1 at lysine 838, which antagonized ubiquitination-mediated degradation. Restoration of AURKA or TRIM28 partially rescued the inhibitory phenotypes induced by SPICE1 silencing. At the downstream level, SPICE1 stabilization was accompanied by increased FASN expression and activation of PI3K/AKT signaling. These findings identify SPICE1 as a pro-metastatic effector in PC and establish the AURKA/TRIM28/SPICE1 axis as a central post-translational mechanism driving bone metastasis. AURKA-mediated phosphorylation licenses TRIM28-dependent SUMOylation, suppresses ubiquitin-mediated degradation, and stabilizes SPICE1. Downstream changes in FASN/PI3K/AKT signaling likely contribute to the malignant phenotype but are secondary to this core regulatory axis.