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NASP Promotes Triple-negative Breast Cancer Progression and Metastasis by Stabilizing YAP in a USP15-Dependent Way

Wenfang Zheng1, Qifeng Luo1, Xuehui Wang1

  • 1Department of Breast and Thyroid Surgery, Shanghai Tenth People's Hospital, School of Medicine, Tongji University, Shanghai, 200072, China.

International Journal of Biological Sciences
|July 4, 2025
PubMed

Insights

Nuclear autoantigenic sperm protein (NASP) drives triple-negative breast cancer (TNBC) metastasis. Targeting NASP or its downstream YAP pathway may offer new therapeutic strategies for TNBC patients with poor prognosis.

Area of Science:

  • Oncology
  • Molecular Biology
  • Cancer Research

Background:

  • Triple-negative breast cancer (TNBC) presents a significant clinical challenge due to its high metastatic potential and poor patient outcomes.
  • Identifying novel molecular mechanisms driving TNBC progression and metastasis is crucial for developing effective therapeutic interventions.

Purpose of the Study:

  • To investigate the role of nuclear autoantigenic sperm protein (NASP) in TNBC progression and metastasis.
  • To elucidate the molecular mechanisms by which NASP influences TNBC aggressiveness.
  • To evaluate NASP as a potential therapeutic target for TNBC.

Main Methods:

  • Analysis of NASP expression levels in TNBC patient samples and correlation with prognosis.
  • Investigating the regulatory mechanism of NASP expression, including the role of SRSF1.
  • Exploring the interaction between NASP, USP15, and YAP.
  • Utilizing in vivo models to validate the functional role of NASP in TNBC growth and metastasis.

Main Results:

  • NASP is highly expressed in TNBC and associated with poor prognosis, functioning as an oncogene.
  • SRSF1 mediates the stabilization of NASP mRNA, leading to its overexpression.
  • NASP enhances USP15 activity, promoting YAP deubiquitylation and stabilization.
  • In vivo studies confirmed NASP's role in promoting TNBC growth and metastasis.

Conclusions:

  • NASP promotes TNBC progression and metastasis by stabilizing YAP through USP15.
  • The NASP/USP15/YAP axis represents a novel pathway implicated in TNBC pathogenesis.
  • Targeting NASP offers a potential therapeutic strategy to improve outcomes for TNBC patients.
Keywords:
NASPUSP15YAPmetastasistriple-negative breast cancer

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