| First Author | Yao ZX | Year | 2010 |
| Journal | J Biol Chem | Volume | 285 |
| Issue | 46 | Pages | 36112-20 |
| PubMed ID | 20739274 | Mgi Jnum | J:166879 |
| Mgi Id | MGI:4849915 | Doi | 10.1074/jbc.M110.162347 |
| Citation | Yao ZX, et al. (2010) Epigenetic silencing of {beta}-spectrin, a TGF-{beta} signaling/scaffolding protein in a human cancer stem cell disorder: Beckwith-Wiedemann syndrome. J Biol Chem 285(46):36112-20 |
| abstractText | Hereditary cancer syndromes provide powerful insights into dysfunctional signaling pathways that lead to sporadic cancers. Beckwith-Wiedemann syndrome (BWS) is a hereditary human cancer stem cell syndrome currently linked to deregulated imprinting at chromosome 11p15 and uniparental disomy. However, causal molecular defects and genetic models have remained elusive to date in the majority of cases. The non-pleckstrin homology domain beta-spectrin (beta2SP) (the official name for human is Spectrin, beta, nonerythrocytic 1 (SPTBN1), isoform 2; the official name for mouse is Spectrin beta 2 (Spnb2), isoform 2), a scaffolding protein, functions as a potent TGF-beta signaling member adaptor in tumor suppression and development. Yet, the role of the beta2SP in human tumor syndromes remains unclear. Here, we report that beta2SP(+/-) mice are born with many phenotypic characteristics observed in BWS patients, suggesting that beta2SP mutant mice phenocopy BWS, and beta2SP loss could be one of the mechanisms associated with BWS. Our results also suggest that epigenetic silencing of beta2SP is a new potential causal factor in human BWS patients. Furthermore, beta2SP(+/-) mice provide an important animal model for BWS, as well as sporadic cancers associated with it, including lethal gastrointestinal and pancreatic cancer. Thus, these studies could lead to further insight into defects generated by dysfunctional stem cells and identification of new treatment strategies and functional markers for the early detection of these lethal cancers that otherwise cannot be detected at an early stage. |
