Reconstitution of TGFBR2-Mediated Signaling Causes Upregulation of GDF-15 in HCT116 Colorectal Cancer Cells
Reconstitution of TGFBR2-Mediated Signaling Causes Upregulation of GDF-15 in HCT116 Colorectal Cancer Cells
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DOI：
10.1371/journal.pone.0131506
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发表时间：
2015-06-26
期刊：
影响因子：
3.7
通讯作者：
Gebert, Johannes
中科院分区：
文献类型：
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作者：
Lee, Jennifer;Fricke, Fabia;Gebert, Johannes
尽管转化生长因子 β 受体 2 型 (TGFBR2) 基因中的失活移码突变被认为是微卫星不稳定 (MSI) 结直肠肿瘤发生的驱动因素，但下游目标蛋白质组的相应改变尚未完全解决。在 MSI 结直肠癌模型细胞系中应用 Click-it 化学蛋白质标记方法与质谱分析相结合，我们鉴定了 21 种从头合成的蛋白质，这些蛋白质在重建 TGFBR2 表达时差异表达。一种候选基因，TGF-β 家族成员生长分化因子-15 (GDF-15)，表现出 TGFBR2 依赖性转录上调，导致细胞内和细胞外蛋白质水平增加。作为一种新的 TGFBR2 靶基因，它可能在 SMAD 介导的信号传导的 TGF-β 分支和 BMP/GDF 分支之间提供联系。
Although inactivating frameshift mutations in the Transforming growth factor beta receptor type 2 (TGFBR2) gene are considered as drivers of microsatellite unstable (MSI) colorectal tumorigenesis, consequential alterations of the downstream target proteome are not resolved completely. Applying a click-it chemistry protein labeling approach combined with mass spectrometry in a MSI colorectal cancer model cell line, we identified 21 de novo synthesized proteins differentially expressed upon reconstituted TGFBR2 expression. One candidate gene, the TGF-beta family member Growth differentiation factor-15 (GDF-15), exhibited TGFBR2-dependent transcriptional upregulation causing increased intracellular and extracellular protein levels. As a new TGFBR2 target gene it may provide a link between the TGF-beta branch and the BMP/GDF branch of SMAD-mediated signaling.