title: Receptor-type Protein tyrosine phosphatase β regulates met phosphorylation and function in head and neck squamous cell carcinoma.
abstract: Head and neck squamous cell carcinoma (HNSCC) is the sixth most common cancer and has a high rate of mortality. Emerging evidence indicates that hepatocyte growth factor receptor (or Met) pathway plays a pivotal role in HNSCC metastasis and resistance to chemotherapy. Met function is dependent on tyrosine phosphorylation that is under direct control by receptor-type protein tyrosine phosphatase β (RPTP-β). We report here that RPTP-β expression is significantly downregulated in HNSCC cells derived from metastatic tumors compared to subject-matched cells from primary tumors. Knockdown of endogenous RPTP-β in HNSCC cells from primary tumor potentiated Met tyrosine phosphorylation, downstream mitogen-activated protein (MAP) kinase pathway activation, cell migration, and invasion. Conversely, restoration of RPTP-β expression in cells from matched metastatic tumor decreased Met tyrosine phosphorylation and downstream functions. Furthermore, we observed that six of eight HNSCC tumors had reduced levels of RPTP-β protein in comparison with normal oral tissues. Collectively, the results demonstrate the importance of RPTP-β in tumor biology of HNSCC through direct dephosphorylation of Met and regulation of downstream signal transduction pathways. Reduced RPTP-β levels, with or without Met overexpression, could promote Met activation in HNSCC tumors.
authors.affiliation: Department of Dermatology, University of Michigan, Ann Arbor, MI 48109-5609, USA. xuyiru@umich.edu
authors.forename: Yiru
authors.initials: Y
authors.lastname: Xu
authors.forename: Jin
authors.initials: J
authors.lastname: Zhou
authors.forename: Thomas E
authors.initials: TE
authors.lastname: Carey
authors.forename: Jonathan B
authors.initials: JB
authors.lastname: McHugh
authors.forename: John J
authors.initials: JJ
authors.lastname: Voorhees
authors.forename: Gary J
authors.initials: GJ
authors.lastname: Fisher
mesh_terms: D002294:Carcinoma, Squamous Cell / Q000235:genetics / Q000378:metabolism*; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000235:genetics; D049109:Cell Proliferation; D015536:Down-Regulation / Q000235:genetics; D006258:Head and Neck Neoplasms / Q000235:genetics / Q000378:metabolism*; D017228:Hepatocyte Growth Factor / Q000494:pharmacology; D006801:Humans; D020935:MAP Kinase Signaling System / Q000187:drug effects; D009361:Neoplasm Invasiveness / Q000235:genetics; D010766:Phosphorylation; D019859:Proto-Oncogene Proteins c-met / Q000235:genetics / Q000378:metabolism*; D054633:Receptor-Like Protein Tyrosine Phosphatases, Class 5 / Q000235:genetics / Q000378:metabolism*; D000077195:Squamous Cell Carcinoma of Head and Neck
chemical_list: D017228:Hepatocyte Growth Factor; D019859:Proto-Oncogene Proteins c-met; D054633:Receptor-Like Protein Tyrosine Phosphatases, Class 5