Abstract 1290: PTEN loss-mediated cell surface translocation of Annexin A2 promotes prostate cancer metastasis

Abstract

Abstract Introduction: Metastasis is a major cause of morbidity in prostate cancer patients. Despite substantial efforts to understand prostate cancer metastasis, the mechanisms involved in preparing the metastatic niche for colonizing the prostate cancer cells are still unknown. Methods/Materials: The normal prostate epithelial and cancer cells were purchased from American Type Culture Collection (Manassas, VA). Immunoblotting, immunofluorescence, flow cytometry, and plasmin generation assay were performed. Results: Our results demonstrated that Pten deletion or mutation caused significantly high phosphorylation of Annexin A2 (AnxA2) at tyrosine-23 in human and murine prostate cancer cell lines compared to the normal prostate epithelial cell lines. However, we did not observe any change in total AnxA2 protein level after Pten deletion/mutation in human and murine prostate cancer cells compared to normal prostate epithelial cells. Our flow cytometry data, immunofluorescence, and membrane wash fraction analysis suggest that AnxA2 expression was higher at the cell surface of Pten null/mutated prostate cancer cell lines compared to the normal prostate epithelial cells. Confocal microscopy and immunoprecipitation analysis revealed that AnxA2 interacts with Pten in normal prostate epithelial cells and inhibits AnxA2 phosphorylation at tyrosine 23. Pten deletion/mutation-mediated translocation of AnxA2 is dependent on the phosphorylation of tyrosine 23, and mutation of tyrosine 23 to a non-phosphomimetic variant inhibits the cell surface translocation process. The cell surface-translocated AnxA2 promotes the plasmin generation in prostate cancer cells, and an AnxA2 inhibitory hexapeptide can neutralize this activity. Conclusions: PTEN loss is the primary driving force for the translocation of AnxA2 to the cell surface and promotes plasmin generation. Citation Format: Pankaj Chaudhary, Christianna Howard-Smith. PTEN loss-mediated cell surface translocation of Annexin A2 promotes prostate cancer metastasis [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 1290.