Krüppel-like factor 4 promotes human osteosarcoma growth and metastasis via regulating CRYAB expression

Oncotarget. 2016 May 24;7(21):30990-1000. doi: 10.18632/oncotarget.8824.

Abstract

Krüppel-like factor 4 (KLF4), a zinc-finger transcription factor, is an essential regulator in many cellular processes, including differentiation, proliferation, inflammation, pluripotency, and apoptosis. Along with these roles in normal cells and tissues, KLF4 has been reported as a tumor suppressor or an oncogene in many cancers. However, the role of KLF4 in osteosarcoma is largely unknown. Here we found the expression of KLF4 was significantly increased in human osteosarcoma tissues compared with the normal tissues. Elevated KLF4 promoted human osteosarcoma cell proliferation and metastasis. Subsequently, mechanistic studies revealed KLF4 specifically bound the promoter of CRYAB and upregulated CRYAB expression in human osteosarcoma cells. Moreover, we found that KLF4 enhanced osteosarcoma cell proliferation and migration via upregulating CRYAB. Therefore, our studies suggested KLF4 may be a potential target for human osteosarcoma therapy.

Keywords: CRYAB; KLF4; migration; osteosarcoma; proliferation.

MeSH terms

  • Animals
  • Bone Neoplasms / metabolism*
  • Bone Neoplasms / pathology
  • Carcinogenesis
  • Cell Differentiation / physiology
  • Cell Line, Tumor
  • Cell Movement / physiology
  • Cell Proliferation / physiology
  • Female
  • Gene Knockdown Techniques
  • Heterografts
  • Humans
  • Kruppel-Like Factor 4
  • Kruppel-Like Transcription Factors / metabolism*
  • Mice
  • Mice, Inbred BALB C
  • Mice, Nude
  • Neoplasm Metastasis
  • Osteosarcoma / metabolism*
  • Osteosarcoma / pathology
  • Transfection
  • Up-Regulation
  • alpha-Crystallin B Chain / biosynthesis*

Substances

  • CRYAB protein, human
  • KLF4 protein, human
  • Klf4 protein, mouse
  • Kruppel-Like Factor 4
  • Kruppel-Like Transcription Factors
  • alpha-Crystallin B Chain