title: PTPRG suppresses tumor growth and invasion via inhibition of Akt signaling in nasopharyngeal carcinoma.
abstract: Protein Tyrosine Phosphatase, Receptor Type G (PTPRG) was identified as a candidate tumor suppressor gene in nasopharyngeal carcinoma (NPC). PTPRG induces significant in vivo tumor suppression in NPC. We identified EGFR as a PTPRG potential interacting partner and examined this interaction. Dephosphorylation of EGFR at EGFR-Y1068 and -Y1086 sites inactivated the PI3K/Akt signaling cascade and subsequent down-regulation of downstream pro-angiogenic and -invasive proteins (VEGF, IL6, and IL8) and suppressed tumor cell proliferation, angiogenesis, and invasion. The effect of Akt inhibition in NPC cells was further validated by Akt knockdown experiments in the PTPRG-down-regulated NPC cell lines. Our results suggested that inhibition of Akt in NPC cells induces tumor suppression at both the in vitro and in vivo levels, and also importantly, in vivo metastasis. In conclusion, we confirmed the vital role of PTPRG in inhibiting Akt signaling with the resultant suppression of in vivo tumorigenesis and metastasis.
authors.affiliation: Department of Clinical Oncology, University of Hong Kong, Hong Kong (SAR), People's Republic of China.|Centre for Cancer Research, University of Hong Kong, Hong Kong (SAR), People's Republic of China.
authors.forename: Arthur Kwok Leung
authors.initials: AK
authors.lastname: Cheung
authors.affiliation: Department of Clinical Oncology, University of Hong Kong, Hong Kong (SAR), People's Republic of China.
authors.forename: Joseph Chok Yan
authors.initials: JC
authors.lastname: Ip
authors.affiliation: Department of Clinical Oncology, University of Hong Kong, Hong Kong (SAR), People's Republic of China.
authors.forename: Adrian Chi Hang
authors.initials: AC
authors.lastname: Chu
authors.affiliation: Department of Clinical Oncology, University of Hong Kong, Hong Kong (SAR), People's Republic of China.|Centre for Cancer Research, University of Hong Kong, Hong Kong (SAR), People's Republic of China.
authors.forename: Yue
authors.initials: Y
authors.lastname: Cheng
authors.affiliation: Department of Clinical Oncology, University of Hong Kong, Hong Kong (SAR), People's Republic of China.
authors.forename: Merrin Man Long
authors.initials: MM
authors.lastname: Leong
authors.affiliation: Department of Clinical Oncology, University of Hong Kong, Hong Kong (SAR), People's Republic of China.
authors.forename: Josephine Mun Yee
authors.initials: JM
authors.lastname: Ko
authors.affiliation: Department of Clinical Oncology, University of Hong Kong, Hong Kong (SAR), People's Republic of China.|Division of Medical Oncology, National Cancer Centre, Singapore.
authors.forename: Wai Ho
authors.initials: WH
authors.lastname: Shuen
authors.affiliation: Department of Clinical Oncology, University of Hong Kong, Hong Kong (SAR), People's Republic of China.|Centre for Cancer Research, University of Hong Kong, Hong Kong (SAR), People's Republic of China.
authors.forename: Hong Lok
authors.initials: HL
authors.lastname: Lung
authors.affiliation: Department of Clinical Oncology, University of Hong Kong, Hong Kong (SAR), People's Republic of China.|Centre for Cancer Research, University of Hong Kong, Hong Kong (SAR), People's Republic of China.|Centre for Nasopharyngeal Carcinoma Research, University of Hong Kong, Hong Kong (SAR), People's Republic of China.
authors.forename: Maria Li
authors.initials: ML
authors.lastname: Lung
mesh_terms: D000818:Animals; D063646:Carcinogenesis; D002277:Carcinoma; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D016147:Genes, Tumor Suppressor; D064593:Heterografts; D006801:Humans; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D000077274:Nasopharyngeal Carcinoma; D009303:Nasopharyngeal Neoplasms / Q000201:enzymology* / Q000235:genetics / Q000473:pathology*; D051057:Proto-Oncogene Proteins c-akt / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism; D054633:Receptor-Like Protein Tyrosine Phosphatases, Class 5 / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction
chemical_list: D051057:Proto-Oncogene Proteins c-akt; C516850:PTPRG protein, human; D054633:Receptor-Like Protein Tyrosine Phosphatases, Class 5
keywords: Akt; EGFR; PTPRG; nasopharyngeal carcinoma; tumor suppressor