Abstract 5579: Identification of MTA1 as a new molecular marker in urothelial carcinoma

Abstract Metastasis-associated protein 1 (MTA1), a master transcriptional co-regulator and chromatin modifier, is strongly associated with many types of clinically aggressive cancers. Loss of MTA1 reduces aggressiveness and metastatic potential in cancer cells. A publicly available human dataset predicts that MTA1 might work as a prognostic marker, however, the exact role of MTA1 in the pathobiology of bladder cancer is unknown. We sought to evaluate the expression of MTA1 and associated epithelial-to-mesenchymal (EMT) events using canine urothelial carcinoma (UC) clinical samples as well as cell lines. We found that MTA1 and cyclooxygenase 2 (COX2) are overexpressed in canine UC samples compared to normal bladder samples, whereas E-cadherin (E-cad) levels are higher in normal bladder. The results of samples demonstrated that MTA1 expression correlated with aggressive clinicopathological features such as high tumor-grade, muscular/vascular invasion, and metastasis. The MTA1 expression differed in tumors depending on their localization, with the highest being in the urethra adjoining the prostate. Unexpectedly, higher E-cad levels were detected in metastatic tumor cells compared to primary tumor cells. Further, we analyzed MTA1 and EMT-associated markers in four invasive canine UC cell lines. Using two cell lines, AxA and SH, and their corresponding MTA1 knockdown (shMTA1) clones, we validated the direct link between MTA1 and these markers on mRNA and protein levels. Overall, these findings suggest that MTA1 may represent a key upstream effector tightly associated with COX2 and EMT-mediated events in canine UC. Accordingly, MTA1 may be considered a feasible interceptive and therapeutic target for canine UC treatment. Citation Format: Gisella Campanelli, Noah Waxner, Nema Parkhomovsky, Raphael Vanderstichel, Ching Yang, Anait S. Levenson. Identification of MTA1 as a new molecular marker in urothelial carcinoma [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 5579.