Tgif1 (thymine-guanine-interacting factor 1) and Tgif2 repress gene expression by binding directly to DNA or interacting with transforming growth factor (TGF) β-responsive SMADs. Tgifs are essential for embryogenesis and may function in tumor progression. By analyzing both gain and loss of Tgif function in a well-established mouse model of intestinal cancer, we show that Tgifs promote adenoma growth in the context of mutant Apc (adenomatous polyposis coli). Despite the tumor-suppressive role of TGFβ signaling, transcriptome profiling of colon tumors suggests minimal effect of Tgifs on the TGFβ pathway. Instead, it appears that Tgifs, which are up-regulated in Apc mutant colon tumors, contribute to reprogramming metabolic gene expression. Integrating gene expression data from colon tumors with other gene expression and chromatin-binding data identifies a set of direct Tgif target genes encoding proteins involved in acetyl CoA and pyruvate metabolism. Analysis of both tumor and nontumor tissues indicates that these genes are targets of Tgif repression in multiple settings, suggesting that this is a core Tgif function. We propose that Tgifs play an important role in regulating basic energy metabolism in normal cells, and that this function of Tgifs is amplified in some cancers.

中文翻译：

---

TGIF转录因子抑制乙酰辅酶A代谢基因的表达并促进肠道肿瘤的生长。

Tgif1（胸腺嘧啶-鸟嘌呤相互作用因子1）和Tgif2通过直接与DNA结合或与转化生长因子（TGF）β反应性SMAD相互作用来抑制基因表达。Tgifs对于胚胎发生至关重要，并且可能在肿瘤进展中起作用。通过分析在成熟的肠道癌小鼠模型中Tgif功能的获得和丧失，我们显示Tgifs在突变Apc（腺瘤性息肉病）的背景下促进腺瘤生长。尽管TGFβ信号通路具有肿瘤抑制作用，但结肠肿瘤的转录组分析表明Tgifs对TGFβ途径的影响极小。取而代之的是，似乎在Apc突变型结肠肿瘤中上调的Tgifs有助于重新编程代谢基因的表达。将来自结肠肿瘤的基因表达数据与其他基因表达和染色质结合数据相结合，可以鉴定出一组直接的Tgif目标基因，这些基因编码了涉及乙酰CoA和丙酮酸代谢的蛋白质。对肿瘤和非肿瘤组织的分析表明，这些基因在多种情况下都是Tgif抑制的靶标，表明这是Tgif的核心功能。我们建议，Tgifs在调节正常细胞中的基本能量代谢中起重要作用，并且在某些癌症中，Tgifs的这一功能得到了放大。