蛋白酪氨酸磷酸酶SHP2在结直肠“炎-癌”中的作用

The function of protein-tyrosine phosphatase SHP2 in inflammation and colorectal cancer

SHP2(SH2 domain-containing protein-tyrosine phosphatase-2)为蛋白酪氨酸磷酸酶,由人PTPN11基因编码,在生长因子、细胞因子的作用下激活ERK/MAPK通路。同时在不同的细胞类型中,SHP2也能够抑制JAK/STAT3通路的激活。SHP2通过调控这两条通路,发挥了不同甚至相反的角色,例如SHP2在乳腺癌、肺癌、头颈部肿瘤中发挥促癌功能,然而在肝癌中抑制了癌症的发生。本文针对SHP2在结直肠中的角色,综述了SHP2在结直肠上皮细胞分化、肠上皮细胞稳态、肠炎、结直肠癌中的功能,以及相关抗肿瘤药物及细胞因子对结直肠癌细胞中SHP2的调控作用。

Protein-tyrosine phosphatase SHP2（SH2 domain-containing protein-tyrosine phosphatase-2）, encoded by the PTPN11 gene in humans, is required for full activation of the ERK/MAPK cascade depending on growth factors and cytokines. Meanwhile in different cell types, SHP2 can inhibit the JAK/STAT3 pathway. By regulating the two pathways, SHP2 plays different even opposite roles, promoting cancer in breast cancer, lung cancer, head and neck cancer but suppressing liver carcinoma progression. This review mainly focuses the role of SHP2 in intestine, summarizing the function of SHP2 in intestinal epithelium differentiating, homeostasis of the intestinal epithelium, colitis, colorectal cancer and the activation of SHP2 by anti-tumor drugs, cytokines in colorectal cancer cells.