Molecular Mechanisms of MTA1-Mediated Progression in Canine Urothelial Carcinoma
Faculty Mentor
Anait S. Levenson
Area of Research
Molecular Biology and Oncology
Major
Biology
Description
Urothelial carcinoma (UC) is the most common form of canine urinary bladder cancer, affecting tens of thousands of dogs each year. Novel targeted therapies are urgently needed for better management of canine UC. In our previous studies, we reported the clinical significance of metastasis-associated protein 1 (MTA1), a master transcriptional regulator responsible for inflammation, tumor growth and metastasis across a wide range of cancers, including canine urothelial carcinoma (UC) (manuscript under review). We found that MTA1 expression was correlated with aggressive clinicopathological features such as high tumor grade, muscular/vascular invasion, and metastasis. We hypothesized that MTA1 may represent a key upstream effector tightly associated with epithelial-to-mesenchymal transition (EMT) events in canine UC. To understand the detailed molecular processes and pathways that drive MTA1-mediated progression of canine UC, we analyzed MTA1 and EMT-associated markers (E-cadherin, Snail, Slug, vimentin, Cyclin D1) in four invasive canine UC cell lines. Using two cell lines, AxA and SH, with high MTA1 expression and their corresponding MTA1 knockdown (shMTA1) clones, we validated the direct link between MTA1 and EMT markers on mRNA and protein levels. Overall, these findings suggest that MTA1 may be considered a feasible interceptive and therapeutic target for canine UC treatment.
Molecular Mechanisms of MTA1-Mediated Progression in Canine Urothelial Carcinoma
Urothelial carcinoma (UC) is the most common form of canine urinary bladder cancer, affecting tens of thousands of dogs each year. Novel targeted therapies are urgently needed for better management of canine UC. In our previous studies, we reported the clinical significance of metastasis-associated protein 1 (MTA1), a master transcriptional regulator responsible for inflammation, tumor growth and metastasis across a wide range of cancers, including canine urothelial carcinoma (UC) (manuscript under review). We found that MTA1 expression was correlated with aggressive clinicopathological features such as high tumor grade, muscular/vascular invasion, and metastasis. We hypothesized that MTA1 may represent a key upstream effector tightly associated with epithelial-to-mesenchymal transition (EMT) events in canine UC. To understand the detailed molecular processes and pathways that drive MTA1-mediated progression of canine UC, we analyzed MTA1 and EMT-associated markers (E-cadherin, Snail, Slug, vimentin, Cyclin D1) in four invasive canine UC cell lines. Using two cell lines, AxA and SH, with high MTA1 expression and their corresponding MTA1 knockdown (shMTA1) clones, we validated the direct link between MTA1 and EMT markers on mRNA and protein levels. Overall, these findings suggest that MTA1 may be considered a feasible interceptive and therapeutic target for canine UC treatment.