Abstract P1-08-05: The mechanism of FOXO3a in coping with oxidative stress to promote TNBC progression

Abstract Triple-negative breast cancer (TNBC) is an aggressive type of breast cancer associated with poor prognosis and limited treatment options. FOXO3a is an important transcription factor participating in many important biological process. It has been reported that FOXO3a expression is associated with lymph node metastasis and poor disease-free survival in TNBC. We also found that overexpression of FOXO3a in MDA-MB-231 cells could promote lung metastasis of by tail vein injection in vivo. However, the mechanism of FOXO3a in TNBC progression remains unclear. Here, we found that FOXO3a was highly expressed in nuclear of TNBC tissues than that in peritumor tissues by immunohistochemistry staining. FOXO3a enhances the invasion and motility of TNBC cells by transwell assays. RNA-sequencing combined bioinformatic analysis suggest that FOXO3a is closely related to adhesion pathway and PI3K/AKT pathway. Considering FOXO3a could translocate to nuclear to activate downstream signaling pathway under oxidative stress. Therefore, we further showed that FOXO3a could activate FAK/PI3K/AKT pathway under oxidative stress to promote TNBC progression. Collectively, our research showed that the expression of nucleus FOXO3a was related to the progression of TNBC, and FAK/PI3K/AKT pathway participate in the role of FOXO3a in promoting the progression of TNBC. FOXO3a may serve as a prognostic biomarker and a potential therapeutic target for TNBC. Citation Format: Manqing Cao. The mechanism of FOXO3a in coping with oxidative stress to promote TNBC progression [abstract]. In: Proceedings of the San Antonio Breast Cancer Symposium 2024; 2024 Dec 10-13; San Antonio, TX. Philadelphia (PA): AACR; Clin Cancer Res 2025;31(12 Suppl):Abstract nr P1-08-05.