TIE1 Promotes Primary Tumor Growth by Inhibiting Apoptosis and Activating the AKT‐p70S6K Signaling Pathway in Breast Cancer

TL;DR

TIE1 promotes breast cancer tumor growth by reducing cell death and activating a key signaling pathway, suggesting it could be a new target for treatment.

Contribution

This study identifies TIE1 as a novel biomarker and potential therapeutic target in Claudin-low breast cancer.

Findings

TIE1 expression correlates with poor prognosis and is elevated in Claudin-low breast cancer.

TIE1 promotes tumorigenicity and activates the AKT–p70S6K pathway in breast cancer cells.

TIE1 cleavage in primary tumors reduces apoptosis and supports cancer cell survival.

Abstract

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.

Highly lung‐metastatic breast‐cancer cells with elevated TIE1 expression exhibit increased tumorigenicity. In primary tumors, TIE1 undergoes cleavage and promotes cancer cell survival by activating the AKT–p70S6K signaling pathway.

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