Proteomic analysis of the regulation of proteins by NO-induced posttranslational modification and anti-cancer therapy

NO抑制癌细胞（胰腺癌和结肠癌细胞）中IGF-IR、EGFR、Akt和IRS-1蛋白表达的磷酸化，但上调Ras/Erk通路。IRS-1蛋白C端是NO诱导IRS-1蛋白泛素化和降解的主要位点。NO抑制胰腺癌、结肠癌和乳腺癌细胞的增殖和侵袭。NO供体和MEK抑制剂的组合增强了这些癌细胞中的抗癌活性。

NO inhibits the phosphorylation of IGF-IR, EGFR, Akt and IRS-1 protein expression, but upregulates Ras/Erk pathway in cancer cells (pancreatic and colon cancer cells). C terminus is responsible site for NO-induced ubiqutination and degradation of IRS-1 protein. NO inhibits the proliferation and invasion of pancreatic, colon and breast cancer cells. Combination of NO-donor and MEK-inhibitor enhances anti-cancer activity in these cancer cells.