<scp>TIE1</scp> Promotes Primary Tumor Growth by Inhibiting Apoptosis and Activating the <scp>AKT</scp> ‐ <scp>p70S6K</scp> Signaling Pathway in Breast Cancer
Triple-negative breast cancer (TNBC) is the most aggressive molecular subtype among all breast cancer types. Its treatment remains a significant challenge due to the lack of clearly defined molecular targets. We previously reported that lung-metastatic cell lines, established via orthotopic transplantation of a TNBC cell line, showed high expression of the TIE1 receptor-tyrosine kinase. In this study, we demonstrated that TIE1 expression correlates with poor prognosis in breast cancer patients and is highly elevated in the Claudin-low subtype, which largely overlaps with TNBC. Notably, TIE1 expression promoted tumorigenicity in a breast cancer cell line. Furthermore, in primary tumors formed by TIE1-expressing cells, we observed TIE1 cleavage, reduced apoptosis, and activation of the AKT-p70S6K signaling pathway. Our findings suggest that TIE1 may serve as a potential molecular target and biomarker for Claudin-low type breast cancer, and further research could have significant implications for its treatment.
Authors
- Kentaro Semba (ORCID: https://orcid.org/0000-0001-7507-8214)
- Kazushi Azuma (ORCID: https://orcid.org/0000-0002-1409-2052)
- Jun Nakayama (ORCID: https://orcid.org/0000-0001-8844-4295)
- Tomohiko Matsuyama (ORCID: https://orcid.org/0000-0003-0862-4988)
- Shinya Watanabe (ORCID: https://orcid.org/0000-0003-1369-9001)
Institutions
- Fukushima Medical University (JP)
- Waseda University (JP)
- Osaka International Cancer Institute (JP)
Publication Details
- Journal
- Genes to Cells
- Published
- 2025-11-01
- DOI
- https://doi.org/10.1111/gtc.70062
- Primary Topic
- Angiogenesis and VEGF in Cancer
- Type
- article
- Field-Weighted Citation Impact
- 0.00
Funders
- Ministry of Education, Culture, Sports, Science and Technology
- Waseda University
- University of Tokyo