PIASy mediates hypoxia-induced SIRT1 transcriptional repression and epithelial-to-mesenchymal transition in ovarian cancer cells

• DOI: 10.1242/jcs.127381
• Publication Date: 2013-07-11T04:46:40Z
• Authors: Lina Sun; He Li; Junliang Chen; Yasumasa Iwasaki; Toru Kubota; Mayumi Matsuoka; Aiguo Shen; Qi Chen; Yong Xu
• Keywords: Hypoxia

Epithelial-mesenchymal transition (EMT) plays an essential role in organogenesis and contributes to a host of pathologies including carcinogenesis. Hypoxia aids tumor metastasis part by promoting EMT cancer cells. The underlying mechanism whereby hypoxia orchestrates remains poorly defined. Here we report that SIRT1, multifaceted player tumorigenesis, opposed ovarian vitro vivo impeding EMT. Hypoxic stress down-regulated SIRT1 expression primarily at the transcriptional level reducing occupancy activator Sp1 on proximal promoter gene SUMOylation dependent manner. Further analysis revealed SUMO E3 ligase PIASy was induced prevented from binding promoter. Conversely, knockdown small interfering RNA (siRNA) restored cells challenged with hypobaric hypoxia, reversed cell EMT, attenuated nude mice. Importantly, human specimen indicated positively, whereas inversely, correlated aggressiveness. In summary, our work has identified novel pathway links down-regulation as such shed light development anti-tumor therapeutics.