Esophageal cancer-related gene 4 at the interface of injury, inflammation, infection, and malignancy.
Esophageal cancer-related gene 4 at the interface of injury, inflammation, infection, and malignancy.
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DOI：
10.2147/gictt.s49085
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发表时间：
2014
期刊：
影响因子：
--
通讯作者：
Eliceiri BP
中科院分区：
文献类型：
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作者：
Baird A;Lee J;Podvin S;Kurabi A;Dang X;Coimbra R;Costantini T;Bansal V;Eliceiri BP
在人类中，食管癌相关基因 4 (ECRG4) 由 2 号染色体 c2orf40 位点的四个外显子编码。ECRG4 信使核糖核酸的翻译产生 148 个氨基酸的分泌型 17 KDa 蛋白质，然后根据表达该基因的细胞，将其加工成 14、10、8、6、4 和 2 个 KDa 肽。由于 c2orf40 位点的高甲基化会抑制许多上皮癌中 ECRG4 基因的表达，因此一些研究人员推测 ECRG4 是一种候选肿瘤抑制因子。事实上，ECRG4 的过度表达会在体外抑制细胞增殖，但除抗肿瘤活性外，它在体内也具有广泛的作用。 ECRG4 过表达会影响细胞凋亡、衰老、细胞迁移、炎症、损伤和感染反应。 ECRG4 活性还取决于其细胞定位、分泌和翻译后处理。这些细胞因子/趋化因子样特征表明，ECRG4 并不是传统的候选肿瘤抑制基因，正如最初通过其在癌症中下调所预测的那样。我们回顾了对 ECRG4 基因表达调控的见解、对其一级结构的了解以及对其新兴生理功能的研究如何结合在一起，以支持 ECRG4 在炎症、感染和恶性肿瘤界面中发挥更复杂的作用。
In humans, esophageal cancer-related gene 4 (ECRG4) is encoded by four exons in the c2orf40 locus of chromosome 2. Translation of ECRG4 messenger ribonucleic acid produces a 148 amino acid-secreted 17 KDa protein that is then processed to 14, ten, eight, six, four, and two KDa peptides, depending on the cell in which the gene is expressed. As hypermethylation at the c2orf40 locus inhibits ECRG4 gene expression in many epithelial cancers, several investigators have speculated that ECRG4 is a candidate tumor suppressor. Indeed, overexpression of ECRG4 inhibits cell proliferation in vitro, but it also has a wide range of effects in vivo beyond its antitumor activity. ECRG4 overexpression affects apoptosis, senescence, cell migration, inflammation, injury, and infection responsiveness. ECRG4 activities also depend on its cellular localization, secretion, and post-translational processing. These cytokine/chemokine-like characteristics argue that ECRG4 is not a traditional candidate tumor suppressor gene, as originally predicted by its downregulation in cancer. We review how insights into the regulation of ECRG4 gene expression, knowledge of its primary structure, and the study of its emerging physiological functions come together to support a much more complex role for ECRG4 at the interface of inflammation, infection, and malignancy.