Mechanistic study of the Tβ4/SLC7A11 signaling pathway regulating breast cancer evolution.

Thymosin β4 (Tβ4) plays a critical role in breast cancer progression, yet its molecular mechanism remains unclear. In this study, we identified that Tβ4 is significantly upregulated in breast cancer tissues and cell lines, and its high expression correlates with poor clinical outcomes. Functionally, Tβ4 promotes breast cancer cell proliferation, migration, epithelial-mesenchymal transition (EMT), and angiogenesis while inhibiting apoptosis. Mechanistically, Tβ4 directly regulates the expression of SLC7A11, a key cystine/glutamate antiporter, thereby enhancing glutathione biosynthesis and suppressing lipid peroxidation to inhibit ferroptosis. Rescue experiments further demonstrated that silencing SLC7A11 abrogates the oncogenic effects of Tβ4 both in vitro and in vivo. Collectively, these findings uncover a novel Tβ4/SLC7A11 axis that modulates ferroptosis sensitivity and contributes to breast cancer malignancy, offering potential therapeutic implications for targeting ferroptosis resistance.