Abstract 359: The Hippo pathway on breast tumor recurrence <and> collateral vulnerability to ferroptosis

Abstract

Abstract Comparing with primary breast tumors, recurrent breast cancers are generally considered more aggressive and incurable. Therefore, novel molecular strategies are urgently needed to target these type of cancers. Here, we report that murine recurrent breast tumor cells are highly susceptible to ferroptosis, a novel form of cell death. Discoidin Domain Receptor Tyrosine Kinase 2 (DDR2), the receptor for collagen I, is upregulated in ferroptosis-sensitive recurrent tumor cells. Ferroptosis inducer, erastin treatment leads to DDR2 upregulation and phosphorylation, independent of collagen I. Furthermore, DDR2 silencing not only prevent ferroptosis but also abolished the robust cell proliferation of murine recurrent tumor cells. Both the ferroptosis protection and reduction of active cell growth may be compatible with the compromised YAP/TAZ upon DDR2 inhibition. Collectively, these findings suggest the role of DDR2 in recurrent breast tumors to drive aggressive cell growth but at the same time reveals its weakness to YAP/TAZ-mediated ferroptosis, providing potential molecular mechanism to target recurrent breast cancers. Citation Format: Chao-Chieh Lin, Jen-Tsan Chi. The Hippo pathway on breast tumor recurrence <and> collateral vulnerability to ferroptosis [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 359.