Abstract 2639: Role of annexin A2 in triple-negative breast cancer metastasis

Introduction: Emerging evidence indicates that AnxA2 plays a role in the invasion and metastasis of breast cancer. However, the clinical significance of AnxA2 expression in breast cancer remains unknown. Methods/Materials: The TNBC cells were purchased from the American Type Culture Collection (Manassas, VA). The expression of AnxA2 in cell lines, tumor tissues, and serum samples of breast cancer patients were analyzed by immunoblotting, immunohistochemistry, and enzyme-linked immunosorbent assay, respectively. Results: We observed that AnxA2 was significantly elevated in the tumor tissues and serum samples of breast cancer patients compared to normal controls. High levels of serum AnxA2 were significantly correlated with tumor grade and poor survival in breast cancer patients. When we analyzed molecular subtypes, we found that AnxA2 expression was notably higher in the tumor tissues and serum samples of triple-negative breast cancer (TNBC) patients compared to those with other breast cancer subtypes. Our studies on breast cancer cell lines indicated that the secretion of AnxA2 is linked to its phosphorylation at tyrosine 23 (Tyr23). Additionally, phosphorylation of AnxA2 at Tyr23 facilitates its translocation to the cell surface in TNBC cell lines. The increased expression of AnxA2 on the cell surface enhances plasmin generation in these cell lines, and an inhibitory hexapeptide against AnxA2 can neutralize this activity. Furthermore, our analysis of AnxA2 phosphorylation in clinical samples confirmed that the phosphorylation at Tyr23 was significantly higher in the tumor tissues of TNBC patients when compared to matched adjacent non-tumorigenic breast tissues. Conclusions: These findings suggest that serum AnxA2 concentration could be a potential diagnostic biomarker for TNBC patients. Citation Format: Pankaj Chaudhary. Role of annexin A2 in triple-negative breast cancer metastasis [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2025; Part 1 (Regular Abstracts); 2025 Apr 25-30; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2025;85(8_Suppl_1):Abstract nr 2639.