4th World Congress on Breast Cancer
Singapore City, singapore
Sudhakar Jha
National University of Singapore, Singapore
Title: TIP60 inhibits epithelial-mesenchymal transition program in breast cancer: A HAT with many tricks
Biography
Biography: Sudhakar Jha
Abstract
HIV-Tat-interacting protein 60 KDa (TIP60) is a lysine acetyltransferase implicated in transcription, DNA damage response and apoptosis. It is known to be downregulated in multiple cancers. Recent studies have shown that TIP60 downregulation correlates with node positivity, metastasis and poor survival rate. Epithelial-mesenchymal transition (EMT) is considered as an important step in cancer metastasis. During this process, there is an overexpression of EMT inducers such as Snail2 (also known as Slug) and repression of cell adhesion molecules such as E-cadherin and EpCAM. Additionally, previous report has demonstrated that E-cadherin and EpCAM expression were repressed by DNA hypermethylation on their promoter region during EMT. In this conference, I will be discussing data that show TIP60 expression partially abrogates cell migration and metastatic potential of breast cancer cells both in vitro and in vivo models. Mechanistically, we show this is through its ability to destabilize DNMT1 and inhibit Snail2 expression. Depletion of TIP60 stabilizes DNMT1 and increase Snail2 level, resulting in the EMT. Activation of DNMT1-Snail2 axis in the absence of TIP60 represses expression of epithelial markers by increased DNA methylation on their promoter region. In pathophysiological scenario, we find TIP60 to be significantly downregulated in breast cancer patients with poor Overall Survival (OS) and Disease-Free Survival (DFS) prognoses. These data suggest that levels of TIP60 can be a prognostic marker of disease progression and stabilization of TIP60 could be a promising strategy to treat cancers.