TrkA promotes MDM2-mediated AGPS ubiquitination and degradation to trigger prostate cancer progression

作者：Yu Zhang, Zhenlin Huang, Keqiang Li, Guoqing Xie, Yuankang Feng, Zihao Wang, Ningyang Li, Ruoyang Liu, Yinghui Ding, Jun Wang, Jinjian Yang, Zhankui Jia · 发表于：Journal of Experimental & Clinical Cancer Research · 年份：2024 · DOI：10.1186/s13046-023-02920-w · 被引用次数：22 · 研究领域：Ferroptosis and cancer prognosis、Cancer-related molecular mechanisms research、Immune cells in cancer

BACKGROUND: As a novel necrosis manner, ferroptosis has been increasingly reported to play a role in tumor progression and treatment, however, the specific mechanisms underlying its development in prostate cancer remain unclear. Growing evidence showed that peroxisome plays a key role in ferroptosis. Herein, we identified a novel mechanism for the involvement of ferroptosis in prostate cancer progression, which may provide a new strategy for clinical treatment of prostate cancer. METHODS: Label-Free Mass spectrometry was used to screen and identify candidate proteins after ferroptosis inducer-ML210 treatment. Immunohistochemistry was undertaken to explore the protein expression of AGPS in prostate cancer tissues compared with normal tissues. Co-immunoprecipitation and GST pull-down were used to identify the directly binding of AGPS to MDM2 in vivo and in vitro. CCK8 assay and colony formation assay were used to illustrate the key role of AGPS in the progression of prostate cancer in vitro. The xenograft model was established to verify the key role of AGPS in the progression of prostate cancer in vivo. RESULTS: AGPS protein expression was downregulated in prostate cancer tissues compared with normal tissues from the first affiliated hospital of Zhengzhou University dataset. Lower expression was correlated with poorer overall survival of patients compared to those with high expression of AGPS. In addition, AGPS can promote ferroptosis by modulating the function of peroxisome-re...