IL-13 receptor α2 stimulates human glioma cell growth and metastasis through the Src/PI3K/Akt/mTOR signaling pathway

Tumour Biol. 2016 Nov;37(11):14701-14709. doi: 10.1007/s13277-016-5346-x. Epub 2016 Sep 14.

Abstract

Glioma is a malignant tumor that affects all kinds of people all over the world. It demonstrates remarkable infiltrative and invasive features. The high expression of interleukin-13 receptor subunit alpha-2 (IL-13Rα2) reportedly plays a pivotal role in some cancers. However, whether IL-13Rα2 contributes to glioma remains unknown. This study demonstrates that IL-13Rα2 is significantly up-regulated in human glioma tissue samples. It is also associated with late stages of disease progression and diminished survival in glioma patients. Gain- and loss-of-function studies demonstrate that IL-13Rα2 promotes the growth, migration, and invasion of glioma cells. In addition, mechanistic investigations show that IL-13Rα2 activates Scr, phosphatidylinositol 3 kinase (PI3K), Akt, and mTOR. Also, restraining Scr in glioma cells attenuates the activation of Scr/PI3K/Akt/mTOR pathway by IL-13Rα2, whereas the silencing of Scr markedly rescues the pro-invasive effect of IL-13Rα2. In conclusion, our results suggest that the high expression of IL-13Rα2 is significantly associated with the growth and metastasis of human glioma cells via the Scr/PI3K/Akt/mTOR pathway, while IL-13Rα2 may be a potential therapeutic target for glioma treatment.

Keywords: Glioma; IL-13Rα2; Invasion; Scr.

MeSH terms

  • Aged
  • Animals
  • Apoptosis
  • Blotting, Western
  • Cell Movement*
  • Cell Proliferation
  • Female
  • Glioma / genetics
  • Glioma / metabolism
  • Glioma / pathology*
  • Humans
  • Immunoenzyme Techniques
  • Interleukin-13 Receptor alpha2 Subunit / genetics
  • Interleukin-13 Receptor alpha2 Subunit / metabolism*
  • Male
  • Mice
  • Mice, Nude
  • Phosphatidylinositol 3-Kinase / genetics
  • Phosphatidylinositol 3-Kinase / metabolism*
  • Proto-Oncogene Proteins c-akt / genetics
  • Proto-Oncogene Proteins c-akt / metabolism*
  • Proto-Oncogene Proteins pp60(c-src) / genetics
  • Proto-Oncogene Proteins pp60(c-src) / metabolism*
  • RNA, Messenger / genetics
  • Real-Time Polymerase Chain Reaction
  • Reverse Transcriptase Polymerase Chain Reaction
  • TOR Serine-Threonine Kinases / genetics
  • TOR Serine-Threonine Kinases / metabolism*
  • Tumor Cells, Cultured
  • Xenograft Model Antitumor Assays

Substances

  • Interleukin-13 Receptor alpha2 Subunit
  • RNA, Messenger
  • MTOR protein, human
  • Phosphatidylinositol 3-Kinase
  • Proto-Oncogene Proteins pp60(c-src)
  • Proto-Oncogene Proteins c-akt
  • TOR Serine-Threonine Kinases