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Targeting RCC1 to block the human soft-tissue sarcoma by disrupting nucleo-cytoplasmic trafficking of Skp2

Mingzhi Zhuang1, Fengyue Li1, Hong Liang2

  • 1College of Biological Science and Engineering, Fuzhou University, Fuzhou, Fujian, 350108, P. R. China.

Cell Death & Disease
|April 1, 2024
PubMed

Insights

Researchers identified RCC1 as an oncogene in soft-tissue sarcomas (STS). Targeting RCC1 inhibits STS growth by disrupting the RCC1-Skp2-p27Kip1 pathway, offering new therapeutic strategies for this malignancy.

Area of Science:

  • Oncology
  • Molecular Biology
  • Biochemistry

Background:

  • Soft-tissue sarcomas (STS) present significant clinical challenges due to genetic complexity, recurrence, and metastasis.
  • Identifying novel therapeutic targets and biomarkers is crucial for improving STS patient outcomes.

Purpose of the Study:

  • To investigate the role of RCC1 (Regulator of Chromosome Condensation 1) as a potential oncogene and therapeutic target in STS.
  • To elucidate the molecular mechanisms underlying RCC1's function in STS progression.

Main Methods:

  • Bioinformatic analysis of RCC1 expression in STS patient data.
  • In vitro functional assays (cell cycle, proliferation, migration) in STS cells.
  • In vivo studies using STS xenograft mouse models.
  • Mechanistic investigations involving protein-protein interactions and degradation pathways.

Main Results:

  • RCC1 is highly expressed in STS and correlates with poor prognosis.
  • RCC1 knockdown inhibits STS cell proliferation, migration, and tumor growth.
  • RCC1 promotes STS oncogenesis by stabilizing Skp2 (S-phase kinase-associated protein 2), leading to p27Kip1 downregulation and G1/S cell cycle progression.
  • RCC1 directly interacts with Skp2, facilitating its nucleo-cytoplasmic trafficking and preventing its degradation.

Conclusions:

  • A novel RCC1-Skp2-p27Kip1 signaling axis is identified as a key driver of STS oncogenesis.
  • RCC1 represents a promising therapeutic target for STS, with potential to improve patient prognosis and treatment strategies.

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