Abstract 2: CAV1-ITGA3 axis attenuates cancer stemness in a preclinical murine model of triple-negative breast cancer

Abstract Triple-negative breast cancer (TNBC) is a notoriously aggressive phenotype with enhanced metastatic and relapse potential. Caveolin-1 (CAV1), a structural component of caveolae is linked to multiple processes involved in primary tumor progression and metastasis. Notably, an upregulation of CAV1 expression level enhances the metastatic capability of TNBC. Previous findings from our lab have demonstrated that CRISPR/Cas9-mediated knockout (KO) of CAV1 mitigates BC metastasis to the lungs in a 4T1 mouse model of mammary carcinoma via integrin alpha 3 (ITGA3) dysregulation. Breast cancer is a heterogenous disease with cancer stem-like cells of high plasticity that recapitulate the primary tumor at a distant metastatic site, CAV1-KO 4T1 cells may likely have an impact on regulation of cancer stemness. In order to investigate this, we evaluated one of the cancer stemness markers, ALDH1A1; pluripotency transcription factors (SOX2, OCT4 and NANOG); and drug efflux transporters (ABCB1, ABCC1, and ABCG2). In support of our hypothesis, data from in vitro CAV1-KO cells and the in vivo CAV1-KO tumors demonstrated a significant downregulation of cancer stemness parameters as compared to control tumors. Based on these findings, we conclude that CAV1-KO may regulate cancer stemness in a 4T1 mouse model of TNBC. Isolation of breast cancer stem cells (BCSCs) based on ALDH1 activity, morphological characterization, and 3D-functional assays will further solidify the role of CAV1 in cancer stemness and its invasive potential. Overall, we identified a novel role for CAV1 in regulating cancer stemness. CAV1-based targeted therapy has tremendous potential to augment treatment outcomes for TNBC. Citation Format: Naveen Chintala Ramulu, Shilpa Thota, Rizwana Begum, Dhirendra Pratap Singh, Biplov Sapkota, Dayanidhi Raman, Joseph Francis. CAV1-ITGA3 axis attenuates cancer stemness in a preclinical murine model of triple-negative breast cancer [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 2.