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

Lin Zhang; Qiwei Pan; Yi Wu; Peng Zhang; Shibao Li; Yuting Xu; Danhua Li; Maojin Zheng; Dongsheng Pei; Qingling Wang

doi:10.1016/j.yexcr.2023.113601

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

Exp Cell Res. 2023 Jun 1;427(1):113601. doi: 10.1016/j.yexcr.2023.113601. Epub 2023 Apr 11.

Authors

Lin Zhang¹, Qiwei Pan², Yi Wu³, Peng Zhang⁴, Shibao Li⁵, Yuting Xu³, Danhua Li³, Maojin Zheng³, Dongsheng Pei⁶, Qingling Wang⁷

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: [email protected].
⁷ Department of Pathology, Xuzhou Medical University, Xuzhou, 221004, Jiangsu, China. Electronic address: [email protected].

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.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Carcinoma, Renal Cell* / pathology
Cell Line
Cell Line, Tumor
Cell Movement
Cell Proliferation
Gene Expression Regulation, Neoplastic
Humans
Kidney Neoplasms* / pathology
Microtubules / metabolism
Polymerization
Receptors, Steroid / metabolism

Substances

Receptors, Steroid