Leucine zipper tumor suppressor 2 inhibits cell proliferation and regulates Lef/Tcf-dependent transcription through Akt/GSK3β signaling pathway in lung cancer

J Histochem Cytochem. 2013 Sep;61(9):659-70. doi: 10.1369/0022155413495875. Epub 2013 Jun 12.

Abstract

Leucine zipper tumor suppressor 2 (LZTS2) is implicated in several cancers; however, its biological mechanisms in non-small cell lung cancer (NSCLC) are not yet understood. We found that low levels of LZTS2 in NSCLC were correlated with tumor and nodal status. LZTS2 could inhibit cell proliferation and cell cycle transition at the G1/S phase and was implicated in the regulation of proteins associated with the canonical Wnt pathway, including GSK3β and β-catenin through inactivating the Akt pathway. These results provide novel mechanistic insight into the biological roles of LZTS2 in lung cancer cells.

Keywords: Akt; GSK3β; LZTS2; NSCLC; β-catenin.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Carcinoma, Non-Small-Cell Lung / genetics*
  • Carcinoma, Non-Small-Cell Lung / metabolism
  • Carcinoma, Non-Small-Cell Lung / pathology
  • Cell Cycle Checkpoints
  • Cell Cycle Proteins / analysis
  • Cell Cycle Proteins / genetics
  • Cell Cycle Proteins / metabolism*
  • Cell Line, Tumor
  • Cell Proliferation
  • DNA-Binding Proteins / analysis
  • DNA-Binding Proteins / genetics
  • DNA-Binding Proteins / metabolism*
  • Down-Regulation
  • Female
  • Gene Expression Regulation, Neoplastic
  • Glycogen Synthase Kinase 3 / metabolism*
  • Glycogen Synthase Kinase 3 beta
  • Humans
  • Lung / metabolism
  • Lung / pathology*
  • Lung Neoplasms / genetics*
  • Lung Neoplasms / metabolism
  • Lung Neoplasms / pathology
  • Male
  • Proteolysis
  • Proto-Oncogene Proteins c-akt / metabolism*
  • Signal Transduction
  • TCF Transcription Factors / metabolism*
  • Transcriptional Activation
  • Tumor Suppressor Proteins / analysis
  • Tumor Suppressor Proteins / genetics
  • Tumor Suppressor Proteins / metabolism*
  • beta Catenin / genetics
  • beta Catenin / metabolism

Substances

  • Cell Cycle Proteins
  • DNA-Binding Proteins
  • LZTS2 protein, human
  • TCF Transcription Factors
  • Tumor Suppressor Proteins
  • beta Catenin
  • GSK3B protein, human
  • Glycogen Synthase Kinase 3 beta
  • Proto-Oncogene Proteins c-akt
  • Glycogen Synthase Kinase 3