PTPRG suppresses tumor growth and invasion via inhibition of Akt signaling in nasopharyngeal carcinoma

Oncotarget. 2015 May 30;6(15):13434-47. doi: 10.18632/oncotarget.3876.


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.

Keywords: Akt; EGFR; PTPRG; nasopharyngeal carcinoma; tumor suppressor.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Carcinogenesis
  • Carcinoma
  • Cell Line, Tumor
  • Cell Proliferation
  • Genes, Tumor Suppressor
  • Heterografts
  • Humans
  • Mice
  • Mice, Inbred BALB C
  • Mice, Nude
  • Nasopharyngeal Carcinoma
  • Nasopharyngeal Neoplasms / enzymology*
  • Nasopharyngeal Neoplasms / genetics
  • Nasopharyngeal Neoplasms / pathology*
  • Proto-Oncogene Proteins c-akt / antagonists & inhibitors*
  • Proto-Oncogene Proteins c-akt / genetics
  • Proto-Oncogene Proteins c-akt / metabolism
  • Receptor-Like Protein Tyrosine Phosphatases, Class 5 / genetics
  • Receptor-Like Protein Tyrosine Phosphatases, Class 5 / metabolism*
  • Signal Transduction


  • Proto-Oncogene Proteins c-akt
  • PTPRG protein, human
  • Receptor-Like Protein Tyrosine Phosphatases, Class 5