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10.1038/oncsis.2016.55

http://scihub22266oqcxt.onion/10.1038/oncsis.2016.55
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suck abstract from ncbi


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pmid27526108
      Oncogenesis 2016 ; 5 (8 ): e254
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  • FLASH protects ZEB1 from degradation and supports cancer cells epithelial-to-mesenchymal transition #MMPMID27526108
  • Abshire CF ; Carroll JL ; Dragoi AM
  • Oncogenesis 2016[Aug]; 5 (8 ): e254 PMID27526108 show ga
  • Cancer metastasis remains a significant challenge and the leading cause of cancer-associated deaths. It is postulated that during metastasis cells undergo epithelial-to-mesenchymal transition (EMT), a process characterized by loss of cell-cell contacts and increased migratory and invasive potential. ZEB1 is one the most prominent transcriptional repressors of genes associated with EMT. We identified caspase-8-associated protein 2 (CASP8AP2 or FLASH) as a novel posttranscriptional regulator of ZEB1. Here we demonstrate that FLASH protects ZEB1 from proteasomal degradation brought by the action of the ubiquitin ligases SIAH1 and F-box protein FBXO45. As a result, loss of FLASH rapidly destabilized ZEB1 and reversed EMT cellular characteristics. Importantly, loss of FLASH blocked transforming growth factor-?-induced EMT and enhanced sensitivity to chemotherapy. Thus, we propose that FLASH-ZEB1 interplay may be a protective mechanism against ZEB1 degradation in cells undergoing EMT and may be an efficacious target for therapies aimed to block EMT progression.
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