Cancer Associated With PTPN11
Patients with a subset of Noonan syndrome PTPN11 mutations also have a higher prevalence of juvenile myelomonocytic leukemias (JMML). Activating Shp2 mutations have also been detected in neuroblastoma, melanoma, acute myeloid leukemia, breast cancer, lung cancer, colorectal cancer. These data suggests that Shp2 may be a proto-oncogene. However, it has been reported that PTPN11/Shp2 can act as either tumor promoter or suppressor. In aged mouse model, hepatocyte-specific deletion of PTPN11/Shp2 promotes inflammatory signaling through the STAT3 pathway and hepatic inflammation/necrosis, resulting in regenerative hyperplasia and spontaneous development of tumors. Decreased PTPN11/Shp2 expression was detected in a subfraction of human hepatocellular carcinoma (HCC) specimens. The bacterium Helicobacter pylori has been associated with gastric cancer, and this is thought to be mediated in part by the interaction of its virulence factor CagA with SHP2.
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