Activation of β-catenin/TCF targets following loss of the tumor suppressor SNF5

肿瘤抑制因子 SNF5 缺失后 β-catenin/TCF 靶标的激活

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作者:E L Mora-Blanco, Y Mishina, E J Tillman, Y-J Cho, C S Thom, S L Pomeroy, W Shao, C W M Roberts

Abstract

The SWI/SNF chromatin remodeling complex is a master regulator of developmental cell-fate decisions, although the key target pathways are poorly characterized. Here, we interrogated the contribution of the SWI/SNF subunit and tumor suppressor SNF5 to the regulation of developmental pathways using conditional mouse and cell culture models. We find that loss of SNF5 phenocopies β-catenin hyperactivation and that SNF5 is essential for regulating Wnt/β-catenin pathway target expression. These data provide insight into chromatin-based mechanisms that underlie developmental regulation and elucidate the emerging theme that mutation of this tumor suppressor complex can activate developmental pathways by uncoupling them from upstream control.

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