2. Academic Validation
  3. GOLM1 promotes prostate cancer progression via interaction with PSMD1 and enhancing AR-driven transcriptional activation

GOLM1 promotes prostate cancer progression via interaction with PSMD1 and enhancing AR-driven transcriptional activation

  • J Cell Mol Med. 2024 Oct;28(20):e70186. doi: 10.1111/jcmm.70186.
Guang Yan 1 2,  Tianhang Zhu 1,  Jiawei Zhou 1,  Xia Li 3,  Zonghua Wen 4,  Bahaerguli Miuhuitijiang 1,  Zhiyong Zhang 1,  Yuejun Du 1,  Chengyao Li 5,  Xiaojun Shi 1,  Wanlong Tan 1
Affiliations

Affiliations

  • 1 Department of Urology, Nanfang Hospital, Southern Medical University, Guangzhou, China.
  • 2 Department of Andrology, Shanghai Seventh People's Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai, China.
  • 3 State Key Laboratory of Holistic Integrative Management of Gastrointestinal Cancers, Department of Biochemistry and Molecular Biology, The Fourth Military Medical University, Xi'an, Shaanxi, China.
  • 4 Department of Pathology, Shenzhen University General Hospital, Shenzhen, China.
  • 5 Department of Transfusion Medicine, School of Laboratory Medicine and Biotechnology, Southern Medical University, Guangzhou, China.
PMID: 39470578 DOI: 10.1111/jcmm.70186
Abstract

Aberrant transcriptional activation of the Androgen Receptor (AR) is a predominant cause of prostate Cancer (PCa), including both in the initial and androgen-independent stages. Our study highlights Golgi membrane protein 1 (GOLM1) as a key regulator of AR-driven transcriptional activity in PCa progression. Utilizing local clinical data and TCGA data, we have established a robust association between GOLM1 and AR target genes, and further demonstrated that GOLM1 can enhance the expression of AR target genes. We discovered that GOLM1 interacts with PSMD1, a component of the 19S regulatory complex in the 26S Proteasome, using mass spectrometry and Co-IP analysis. It is well known that ubiquitin-proteasome plays a vital role in AR expression and transcriptional regulation. Our findings demonstrate that GOLM1 enhances ubiquitin Proteasome activity by binding to PSMD1, thereby facilitating AR-driven transcriptional activity and PCa progression. These results indicate that GOLM1 and its associated proteins may become potential therapeutic targets for PCa characterized by dysregulated AR-driven transcriptional activation.

Keywords

AR; GOLM1; PSMD1; UPS; prostate cancer.

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