Article

Cancer and Metastasis Reviews

, Volume 27, Issue 2, pp 179-192

First online:

The tyrosine phosphatase Shp2 (PTPN11) in cancer

  • Gordon ChanAffiliated withOntario Cancer Institute Email author 
  • , Demetrios KalaitzidisAffiliated withBeth Israel Deaconess Medical Center, Harvard Medical School
  • , Benjamin G. NeelAffiliated withOntario Cancer Institute

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Abstract

Diverse cellular processes are regulated by tyrosyl phosphorylation, which is controlled by protein-tyrosine kinases (PTKs) and protein-tyrosine phosphatases (PTPs). De-regulated tyrosyl phosphorylation, evoked by gain-of-function mutations and/or over-expression of PTKs, contributes to the pathogenesis of many cancers and other human diseases. PTPs, because they oppose the action of PTKs, had been considered to be prime suspects for potential tumor suppressor genes. Surprisingly, few, if any, tumor suppressor PTPs have been identified. However, the Src homology-2 domain-containing phosphatase Shp2 (encoded by PTPN11) is a bona fide proto-oncogene. Germline mutations in PTPN11 cause Noonan and LEOPARD syndromes, whereas somatic PTPN11 mutations occur in several types of hematologic malignancies, most notably juvenile myelomonocytic leukemia and, more rarely, in solid tumors. Shp2 also is an essential component in several other oncogene signaling pathways. Elucidation of the events underlying Shp2-evoked transformation may provide new insights into oncogenic mechanisms and novel targets for anti-cancer therapy.

Keywords

Shp2 Shp-2 PTPN11 Protein-tyrosine phosphatase (PTP) Leukemia Juvenile myelomonocytic leukemia (JMML) Noonan syndrome Cancer Signal transduction Helicobacter pylori Breast cancer