Abstract:
:HIV-Tat-interacting protein of 60 kDa (TIP60) is a lysine acetyltransferase and known to be downregulated in multiple cancers. Among various signalling pathways, TIP60 is implicated in regulating epithelial-mesenchymal transition (EMT). Here, we show that TIP60 expression abrogates cell migration and metastatic potential of breast cancer cells using in vitro and in vivo models. Mechanistically, we show that this is through its ability to destabilize DNMT1 and inhibit SNAIL2 function (SNAIL2-mediated EMT/cell migration). Depletion of TIP60 stabilizes DNMT1 and increases SNAIL2 levels, resulting in EMT. Recruitment of DNMT1 to the SNAIL2 targets in the absence of TIP60 increases DNA methylation on their promoter region and further represses the expression of epithelial markers. In pathophysiological scenario, we find TIP60 to be significantly downregulated in breast cancer patients with poor overall survival and disease-free survival prognoses. These data suggest that levels of TIP60 can be a prognostic marker of breast cancer progression and stabilization of TIP60 could be a promising strategy to treat cancers.
journal_name
J Mol Cell Bioljournal_title
Journal of molecular cell biologyauthors
Zhang Y,Subbaiah VK,Rajagopalan D,Tham CY,Abdullah LN,Toh TB,Gong M,Tan TZ,Jadhav SP,Pandey AK,Karnani N,Chow EK,Thiery JP,Jha Sdoi
10.1093/jmcb/mjw038subject
Has Abstractpub_date
2016-10-01 00:00:00pages
384-399issue
5eissn
1674-2788issn
1759-4685pii
mjw038journal_volume
8pub_type
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