AURKA phosphorylation licenses TRIM28-dependent SUMOylation to stabilize SPICE1 in prostate cancer bone metastasis
5 affiliations
- 1Department of Geriatrics & Orthopedics, The Third Affiliated Hospital,Jiangxi Medical College, Nanchang University, Nanchang, 330006 China
- 2Jiangxi Provincial Key Laboratory of Spine and Spinal Cord Diseases, Nanchang, 330006 People’s Republic of China
- 3Institute of Spinal Cord Disease, Nanchang University, Nanchang, 330006 People’s Republic of China
- 4Postdoctoral Innovation Practice Base, The First Affiliated Hospital, Jiangxi Medical College, Nanchang University, Nanchang, 330006 People’s Republic of China
- 5Department of Orthopedics, the 908th Hospital of Chinese People’s Liberation Army Joint Logistics Support Force, Nanchang, 330002 People’s Republic of China
Abstract
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.
Supplementary Information: The online version contains supplementary material available at https://doi.org/10.1007/s00018-026-06396-7.
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BibTeX
@article{jiang2026aurka,
title = {{AURKA phosphorylation licenses TRIM28-dependent SUMOylation to stabilize SPICE1 in prostate cancer bone metastasis}},
author = {Haoxin Jiang and Weilai Tong and Shijiang Wang and Xu Xiong and Geliang Yao and Feng Yang and Yi Xu and Jiaming Liu and Xinsheng Xie and Zhili Liu},
journal = {Cellular and Molecular Life Sciences: CMLS},
year = {2026},
month = sep,
doi = {10.1007/s00018-026-06396-7},
url = {https://doi.org/10.1007/s00018-026-06396-7},
note = {CC BY-NC-ND 4.0},
}
RIS
TY - JOUR
TI - AURKA phosphorylation licenses TRIM28-dependent SUMOylation to stabilize SPICE1 in prostate cancer bone metastasis
AU - Haoxin Jiang
AU - Weilai Tong
AU - Shijiang Wang
AU - Xu Xiong
AU - Geliang Yao
AU - Feng Yang
AU - Yi Xu
AU - Jiaming Liu
AU - Xinsheng Xie
AU - Zhili Liu
PY - 2026
DA - 2026/09/01
JO - Cellular and Molecular Life Sciences: CMLS
DO - 10.1007/s00018-026-06396-7
UR - https://doi.org/10.1007/s00018-026-06396-7
AB - 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. Supplementary Information: The online version contains supplementary material available at https://doi.org/10.1007/s00018-026-06396-7.
SN - 1420-682X
SN - 1420-9071
ER -