2. Academic Validation
  3. ORP8 inhibits renal cell carcinoma progression by accelerating Stathmin1 degradation and microtubule polymerization

ORP8 inhibits renal cell carcinoma progression by accelerating Stathmin1 degradation and microtubule polymerization

  • Exp Cell Res. 2023 Apr 11;427(1):113601. doi: 10.1016/j.yexcr.2023.113601.
Lin Zhang 1,  Qiwei Pan 2,  Yi Wu 3,  Peng Zhang 4,  Shibao Li 5,  Yuting Xu 3,  Danhua Li 3,  Maojin Zheng 3,  Dongsheng Pei 6,  Qingling Wang 7
Affiliations

Affiliations

  • 1 Department of Pathology, Xuzhou Medical University, Xuzhou, 221004, Jiangsu, China; Jiangsu Province Key Laboratory of Anesthesiology, Xuzhou Medical University, Xuzhou, 221004, Jiangsu, China.
  • 2 Department of Pathology, Xuzhou Medical University, Xuzhou, 221004, Jiangsu, China; Taizhou Hospital of Zhejiang, Taizhou, 317000, Zhejiang, China.
  • 3 Department of Pathology, Xuzhou Medical University, Xuzhou, 221004, Jiangsu, China.
  • 4 Department of Pathogenic Biology and Immunology, Xuzhou Medical University, Xuzhou, 221004, Jiangsu, China.
  • 5 Department of Laboratory Medicine, Affiliated Hospital of Xuzhou Medical University, Xuzhou, Jiangsu, China.
  • 6 Department of Pathology, Xuzhou Medical University, Xuzhou, 221004, Jiangsu, China. Electronic address: dspei@xzhmu.edu.cn.
  • 7 Department of Pathology, Xuzhou Medical University, Xuzhou, 221004, Jiangsu, China. Electronic address: qlwang@xzhmu.edu.cn.
PMID: 37054771 DOI: 10.1016/j.yexcr.2023.113601
Abstract

ORP8 has been reported to suppress tumor progression in various malignancies. However, the functions and underlying mechanisms of ORP8 are still unknown in renal cell carcinoma (RCC). Here, decreased expression of ORP8 was detected in RCC tissues and cell lines. Functional assays verified that ORP8 suppressed RCC cell growth, migration, invasion, and metastasis. Mechanistically, ORP8 attenuated Stathmin1 expression by accelerating ubiquitin-mediated proteasomal degradation and led to an increase in microtubule polymerization. Lastly, ORP8 knockdown partly rescued microtubule polymerization, as well as aggressive cell phenotypes induced by paclitaxel. Our findings elucidated that ORP8 suppressed the malignant progression of RCC by increasing Stathmin1 degradation and microtubule polymerization, thus suggesting that ORP8 might be a novel target for the treatment of RCC.

Keywords

Microtubule polymerization; ORP8; RCC; Stathmin1; Ubiquitination.

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