Effect of HDAC Inhibitor on Mesenchymal to Epithelial Transition (MET) in Non-Small Lung Cancer Cells (NSCLC)
Abstract
The epithelial to mesenchymal transition (EMT) is a highly dynamic process. It is also involved in enhancing the tumor invasiveness and metastasis of the cancer cells. Therefore, the generation of tumor cells with stem cell properties plays a significant role in developing resistance to cancer treatment. The reversal of EMT to MET (mesenchymal to epithelial transition) is poorly understood at the present time. Increased mesenchymal marker levels have been associated with increased lung cancer risk. We hypothesized that suberoyl-anilide hydroxamic acid (SAHA, also known as Vorinostat) might promote MET through epigenetic modification such as acetylation and methylation. We analyzed both EMT and epigenetic marker expressions in H460 and HCC827 lung cell lines. Our microarray data revealed that SAHA treatment reduced the methylation of DNA and histones. We confirmed the decrease in DNMT3A, SUV39H1, and PRMT1 levels in lung cancer cells. Furthermore, we analyzed the stable overexpression of E-cadherin and acetylated histones in both lung cancer cells following SAHA treatment. The results showed that the reversal of EMT to MET process did correlate with epigenetic alterations induced by SAHA. We further demonstrated that hyperacetylation and hypomethylations were associated with significant induction of MET indicated by higher E-cadherin levels and lower vimentin levels when compared to control cells. Further studies are underway to fully determine the intracellular interplay of these mechanisms. (This project was supported by The Royal Dames of Cancer Research Inc., Ft. Lauderdale, Florida).
Faculty Sponsors
Dr. Umamaheswari Natarajan, Dr. Thiagarajan Venkatesan, Dr. Mir Saleem, Dr. Appu Rathinavelu
Project Type
Event
Location
Alvin Sherman Library
Start Date
4-6-2021 12:00 PM
End Date
4-9-2021 12:00 PM
Effect of HDAC Inhibitor on Mesenchymal to Epithelial Transition (MET) in Non-Small Lung Cancer Cells (NSCLC)
Alvin Sherman Library
The epithelial to mesenchymal transition (EMT) is a highly dynamic process. It is also involved in enhancing the tumor invasiveness and metastasis of the cancer cells. Therefore, the generation of tumor cells with stem cell properties plays a significant role in developing resistance to cancer treatment. The reversal of EMT to MET (mesenchymal to epithelial transition) is poorly understood at the present time. Increased mesenchymal marker levels have been associated with increased lung cancer risk. We hypothesized that suberoyl-anilide hydroxamic acid (SAHA, also known as Vorinostat) might promote MET through epigenetic modification such as acetylation and methylation. We analyzed both EMT and epigenetic marker expressions in H460 and HCC827 lung cell lines. Our microarray data revealed that SAHA treatment reduced the methylation of DNA and histones. We confirmed the decrease in DNMT3A, SUV39H1, and PRMT1 levels in lung cancer cells. Furthermore, we analyzed the stable overexpression of E-cadherin and acetylated histones in both lung cancer cells following SAHA treatment. The results showed that the reversal of EMT to MET process did correlate with epigenetic alterations induced by SAHA. We further demonstrated that hyperacetylation and hypomethylations were associated with significant induction of MET indicated by higher E-cadherin levels and lower vimentin levels when compared to control cells. Further studies are underway to fully determine the intracellular interplay of these mechanisms. (This project was supported by The Royal Dames of Cancer Research Inc., Ft. Lauderdale, Florida).
