文章：

幽门螺杆菌CagA蛋白的致癌机制

Oncogenic mechanisms of the Helicobacter pylori CagA protein

原文发布日期：2004-09-01

DOI: 10.1038/nrc1433

类型: Review Article

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要点：

1. Gastric carcinoma is the second most common cause of cancer-related death worldwide. Chronic infection with Helicobacter pylori that carries the cytotoxin-associated antigen A (cagA) gene is associated with gastric carcinoma.
2. The cagA gene product, CagA, is delivered into gastric epithelial cells by the bacterial type IV secretion system and undergoes tyrosine phosphorylation by SRC family kinases. Tyrosine phosphorylation occurs at EPIYA motifs on CagA.
3. Phosphorylated CagA specifically binds and activates SHP2, the first phosphatase found to act as a human oncoprotein.
4. As SHP2 transmits positive signals for cell growth and motility, deregulation of SHP2 by CagA is an important mechanism by which cagA-positive H. pylori promotes gastric carcinogenesis.
5. CagA is noted for its variation at the SHP2 binding site and, based on the sequence variation, is subclassified into two main types — East-Asian CagA and Western CagA. East-Asian CagA shows stronger SHP2 binding and greater biological activity than Western CagA.
6. In East-Asian countries, endemic circulation of H. pylori strains that carry biologically active forms of CagA might underlie the high incidence of gastric carcinoma.

要点翻译：

1. 胃癌是全球癌症相关死亡的第二大常见原因。携带细胞毒素相关抗原A（cagA）基因的幽门螺杆菌慢性感染与胃癌的发生相关。
2. cagA基因产物CagA通过细菌IV型分泌系统被递送至胃上皮细胞内，并经由SRC家族激酶发生酪氨酸磷酸化。该磷酸化作用发生于CagA的EPIYA基序。
3. 磷酸化CagA特异性结合并激活SHP2——首个被证实作为人类癌蛋白发挥作用的磷酸酶。由于SHP2传递促进细胞生长和运动的正向信号，CagA对SHP2的失调作用成为cagA阳性幽门螺杆菌促进胃癌发生的重要机制。
4. CagA在其SHP2结合位点具有多样性特征，根据序列差异主要可分为两大亚型：东亚型CagA和西方型CagA。东亚型CagA较西方型具有更强的SHP2结合能力和更高的生物活性。
5. 在东亚国家，携带高生物活性CagA的幽门螺杆菌菌株的地方性流行可能是该地区胃癌高发的重要基础。

英文摘要：

Infection with strains of Helicobacter pylori that carry the cytotoxin-associated antigen A (cagA) gene is associated with gastric carcinoma. Recent studies have shed light on the mechanism through which the cagA gene product, CagA, elicits pathophysiological actions. CagA is delivered into gastric epithelial cells by the bacterial type IV secretion system, where it deregulates the SHP2 oncoprotein. Intriguingly, CagA is noted for its variation, particularly at the SHP2-binding site, which could affect the potential of different strains of H. pylori to promote gastric carcinogenesis.

摘要翻译： 

感染携带细胞毒素相关抗原A（cagA）基因的幽门螺杆菌菌株与胃癌相关。最新研究阐明了cagA基因产物CagA引发病理生理作用的机制：CagA通过细菌Ⅳ型分泌系统被递送至胃上皮细胞内，进而扰乱SHP2癌蛋白的功能。值得注意的是，CagA存在变异，尤其在其SHP2结合位点，这种差异可能影响不同幽门螺杆菌菌株促发胃癌的潜能。

原文链接：

Oncogenic mechanisms of the Helicobacter pylori CagA protein