Interleukin 7 receptor activates PI3K/Akt/mTOR signaling pathway via downregulation of Beclin-1 in lung cancer

Mol Carcinog. 2019 Mar;58(3):358-365. doi: 10.1002/mc.22933. Epub 2018 Dec 5.

Abstract

Interleukin-7(IL-7) can regulate proliferation and apoptosis of cell and also regulate tumor lymphangiogenesis, but whether it regulating autophagy of tumor cells is not well known. We study the relationship between IL-7 and some autophagy-related markers, Beclin 1 and mammalian target of rapamycin (mTOR) and the mechanism of IL-7 in regulating autophagy of human lung cancer cells. We detected expression of Beclin 1 and mTOR in lung cancer cells and their impact on the prognosis of lung cancer patients. Using Western blot and Reverse Transcription PCR, we found that IL-7 activates PI3 K/Akt/mTOR signaling pathway by downregulated the expression of Beclin 1 in lung cancer cell lines. In addition, the expressions of Beclin 1 and mTOR were well correlated with clinical stages and survival of human non-small cell lung cancer (NSCLC) patients. IL-7R, mTOR, and tumor stage were the independent prognosticators in lung cancer. Taken together, our results provided evidence that IL-7 activates PI3 K/Akt/mTOR signaling pathway via Beclin 1 to regulate autophagy in lung cancer cells.

Keywords: Beclin 1; Interleukin-7 Receptor; Interleukin7; lung cancer; mTOR.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenocarcinoma / metabolism
  • Adenocarcinoma / secondary
  • Adenocarcinoma / therapy
  • Apoptosis
  • Beclin-1 / genetics
  • Beclin-1 / metabolism*
  • Biomarkers, Tumor / genetics
  • Biomarkers, Tumor / metabolism
  • Carcinoma, Non-Small-Cell Lung / metabolism
  • Carcinoma, Non-Small-Cell Lung / pathology*
  • Carcinoma, Non-Small-Cell Lung / therapy
  • Carcinoma, Squamous Cell / metabolism
  • Carcinoma, Squamous Cell / secondary
  • Carcinoma, Squamous Cell / therapy
  • Cell Proliferation
  • Female
  • Follow-Up Studies
  • Gene Expression Regulation, Neoplastic
  • Humans
  • Interleukin-7 Receptor alpha Subunit / genetics
  • Interleukin-7 Receptor alpha Subunit / metabolism*
  • Lung Neoplasms / metabolism
  • Lung Neoplasms / pathology*
  • Lung Neoplasms / therapy
  • Male
  • Middle Aged
  • Neoplasm Metastasis
  • Neoplasm Recurrence, Local / metabolism
  • Neoplasm Recurrence, Local / pathology
  • Neoplasm Recurrence, Local / therapy
  • Phosphatidylinositol 3-Kinases / genetics
  • Phosphatidylinositol 3-Kinases / metabolism*
  • Prognosis
  • Proto-Oncogene Proteins c-akt / genetics
  • Proto-Oncogene Proteins c-akt / metabolism
  • Survival Rate
  • TOR Serine-Threonine Kinases / genetics
  • TOR Serine-Threonine Kinases / metabolism
  • Tumor Cells, Cultured

Substances

  • BECN1 protein, human
  • Beclin-1
  • Biomarkers, Tumor
  • IL7R protein, human
  • Interleukin-7 Receptor alpha Subunit
  • MTOR protein, human
  • AKT1 protein, human
  • Proto-Oncogene Proteins c-akt
  • TOR Serine-Threonine Kinases