STEAP3 promotes triple-negative breast cancer growth through the FGFR1-mediated activation of PI3K/AKT/mTOR signaling

IF 4.6 2区综合性期刊 Q1 MULTIDISCIPLINARY SCIENCES

iScience Pub Date : 2025-04-24 DOI:10.1016/j.isci.2025.112526

Lifang Yuan , Yuhan Bao , Junbao Liu , Ping Sun

引用次数: 0

Abstract

Triple-negative breast cancer (TNBC) is a highly aggressive subtype with a poor prognosis and lacks effective targeted therapies. Six-transmembrane epithelial antigen of prostate 3(STEAP3) is specifically overexpressed in TNBC, but its precise role and molecular mechanisms remain unclear. Here, we show that STEAP3 is positively correlated with proliferation markers in TNBC, but not in non-TNBC. Further assays revealed that STEAP3 significantly enhances TNBC cell proliferation, invasion, and metastasis in vitro. Mechanistically, STEAP3 promotes TNBC progression by stabilizing FGFR1 and subsequently activating the PI3K/AKT/mTOR pathway. In xenograft models, STEAP3 knockdown suppressed tumor growth and reduced the expression of proliferation markers, consistent with in vitro findings. These results demonstrate STEAP3 as a key regulator of TNBC progression via FGFR1-mediated PI3K/AKT/mTOR signaling and highlight its potential as a promising therapeutic target.

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STEAP3通过fgfr1介导的PI3K/AKT/mTOR信号的激活促进三阴性乳腺癌的生长

三阴性乳腺癌（TNBC）是一种高度侵袭性的亚型，预后差，缺乏有效的靶向治疗。前列腺3六跨膜上皮抗原（STEAP3）在TNBC中特异性过表达，但其确切作用和分子机制尚不清楚。在这里，我们发现STEAP3在TNBC中与增殖标志物呈正相关，而在非TNBC中则不然。进一步的实验表明，STEAP3显著增强TNBC细胞的增殖、侵袭和转移。从机制上讲，STEAP3通过稳定FGFR1并随后激活PI3K/AKT/mTOR通路来促进TNBC的进展。在异种移植物模型中，STEAP3敲低抑制肿瘤生长并降低增殖标志物的表达，与体外研究结果一致。这些结果表明STEAP3是通过fgfr1介导的PI3K/AKT/mTOR信号传导介导TNBC进展的关键调节剂，并强调其作为有希望的治疗靶点的潜力。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

iScience Multidisciplinary-Multidisciplinary

CiteScore

7.20

自引率

1.70%

发文量

1972

审稿时长

6 weeks

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