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

## TL;DR

This study shows that NASP promotes the spread of triple-negative breast cancer by stabilizing YAP through USP15, offering new therapeutic insights.

## Contribution

The novel finding is that NASP promotes TNBC progression via a USP15-dependent stabilization of YAP.

## Key findings

- High NASP expression in TNBC correlates with poor patient prognosis.
- NASP stabilizes YAP by enhancing USP15 activity, reducing YAP ubiquitination.
- In vivo experiments confirm NASP's role in TNBC growth and metastasis.

## Abstract

Triple-negative breast cancer (TNBC) was a subtype of breast cancer with high rate of metastasis and poor prognosis. Thus, it is urgent to explore the underlying mechanism of TNBC metastasis and seek for potential therapeutic targets to improve the prognosis of TNBC patients. Here we reported that nuclear autoantigenic sperm protein (NASP) was highly expressed in TNBC and related to poor prognosis of TNBC patients. NASP acted as an oncogene that promoted the progression and metastasis of TNBC. Mechanistically, high expression of NASP in TNBC was induced by SRSF1-mediated stabilization of NASP mRNA. NASP interacted with USP15 and facilitated its activity, which resulted in the deubiquitylation and stabilization of YAP by erasing K48-linked polyubiquitination. Moreover, in vivo studies validated the role of NASP in stimulating TNBC growth and metastasis. Altogether, NASP promoted TNBC progression and metastasis by stabilizing YAP in a USP15-dependent way. It might provide new insights and potential therapeutic targets for preventing TNBC metastasis and improving the prognosis of TNBC patients.