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

Lin Zhang1, Qiwei Pan2, Yi Wu3

  • 1Department of Pathology, Xuzhou Medical University, Xuzhou, 221004, Jiangsu, China; Jiangsu Province Key Laboratory of Anesthesiology, Xuzhou Medical University, Xuzhou, 221004, Jiangsu, China.

Experimental Cell Research
|April 13, 2023
PubMed

Insights

Oxysterol-binding protein homolog 8 (ORP8) suppresses renal cell carcinoma (RCC) progression by degrading Stathmin1, enhancing microtubule polymerization. This suggests ORP8 as a potential therapeutic target for RCC treatment.

Area of Science:

  • Oncology
  • Molecular Biology
  • Biochemistry

Background:

  • Oxysterol-binding protein homolog 8 (ORP8) is recognized for its tumor-suppressive roles in various cancers.
  • The specific functions and molecular mechanisms of ORP8 in renal cell carcinoma (RCC) remain largely uncharacterized.

Purpose of the Study:

  • To investigate the expression levels of ORP8 in RCC.
  • To elucidate the functional role of ORP8 in RCC progression.
  • To uncover the underlying molecular mechanisms by which ORP8 affects RCC malignancy.

Main Methods:

  • Quantitative analysis of ORP8 expression in RCC tissues and cell lines.
  • In vitro functional assays to assess the impact of ORP8 on cell growth, migration, invasion, and metastasis.
  • Mechanistic studies involving ubiquitin-proteasome pathway analysis and microtubule polymerization assays.
  • Assessment of ORP8's role in paclitaxel-induced cellular responses.

Main Results:

  • ORP8 expression was found to be decreased in RCC tissues and cell lines compared to normal controls.
  • Overexpression of ORP8 significantly inhibited RCC cell growth, migration, invasion, and metastasis.
  • ORP8 was shown to reduce Stathmin1 levels by promoting its ubiquitin-mediated proteasomal degradation.
  • This degradation led to increased microtubule polymerization, thereby suppressing RCC progression.
  • Knockdown of ORP8 partially reversed the effects on microtubule polymerization and paclitaxel-induced aggressive phenotypes.

Conclusions:

  • ORP8 acts as a tumor suppressor in renal cell carcinoma.
  • The mechanism involves the acceleration of Stathmin1 degradation, leading to enhanced microtubule polymerization.
  • ORP8 represents a promising novel therapeutic target for the treatment of RCC.
Keywords:
Microtubule polymerizationORP8RCCStathmin1Ubiquitination

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