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

Summary: 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. H...

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Bibliographic Details
Main Authors: Lifang Yuan, Yuhan Bao, Junbao Liu, Ping Sun
Format: Article
Language:English
Published: Elsevier 2025-06-01
Series:iScience
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Online Access:http://www.sciencedirect.com/science/article/pii/S2589004225007874
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Summary:Summary: 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.
ISSN:2589-0042