Progenitor expansion in apc mutants is mediated by Jak/Stat signaling.
Progenitor expansion in apc mutants is mediated by Jak/Stat signaling.
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DOI：
10.1186/1471-213x-11-73
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发表时间：
2011-12-02
影响因子：
--
通讯作者：
Dorsky RI
中科院分区：
文献类型：
--
作者：
Lin J;Wang X;Dorsky RI
APC是Wnt/ß-catenin通路的负调节因子，其突变可导致癌症和严重的发育缺陷。在这两种情况下，受影响的细胞采用增殖祖细胞状态，不能分化。虽然Wnt/ß-catenin信号的一些靶基因的上调已被证明在个体组织中介导这些表型，但尚不清楚APC突变体中的缺陷是否存在共同的机制。在这里，我们发现stat3，一种已知的致癌基因和多个组织中ß-catenin的靶标，在apc突变斑马鱼胚胎中上调。我们进一步证明，在apc突变体中观察到，Jak/Stat信号是增加增殖水平和神经祖基因表达水平所必需的。总之，我们的数据表明，Jak/Stat信号的调控可能代表了一种保守的机制，解释了APC突变下游未分化细胞的扩增。
Mutations in APC, a negative regulator of the Wnt/ß-catenin pathway, can cause cancer as well as profound developmental defects. In both cases, affected cells adopt a proliferative progenitor state and fail to differentiate. While the upregulation of some target genes of Wnt/ß-catenin signaling has been shown to mediate these phenotypes in individual tissues, it is unclear whether a common mechanism underlies the defects in APC mutants. Here we show that stat3, a known oncogene and a target of ß-catenin in multiple tissues, is upregulated in apc mutant zebrafish embryos. We further demonstrate that Jak/Stat signaling is necessary for the increased level of proliferation and neural progenitor gene expression observed in apc mutants. Together, our data suggest that the regulation of Jak/Stat signaling may represent a conserved mechanism explaining the expansion of undifferentiated cells downstream of APC mutations.