ILEI Drives Epithelial to Mesenchymal Transition and Metastatic Progression in the Lung Cancer Cell Line A549

Tumour Biol. 2014 Feb;35(2):1377-82. doi: 10.1007/s13277-013-1188-y. Epub 2013 Sep 27.

Abstract

Transforming growth factor beta (TGF-β) induces epithelial-mesenchymal transition (EMT) accompanied by cellular differentiation and migration. Despite extensive transcriptomic profiling, identification of TGF-β-inducible, EMT-specific genes during metastatic progression of lung cancer remains elusive. Here, we functionally validate a previously described post-transcriptional pathway by which TGF-β modulates expression of interleukin-like EMT inducer (ILEI), and EMT itself. We show that poly r(C)-binding protein 1 (PCBP1) binds ILEI transcript and repress its translation. TGF-β activation leads to phosphorylation at serine-43 of PCBP1 by protein kinase Bβ/Akt2, inducing its release from the ILEI transcript and translational activation. Modulation of hnRNP E1 expression modification altered TGF-β-mediated reversal of translational silencing of ILEI transcripts and EMT. Furthermore, ILEI could induce, as well as maintain, CD24(low)CD44(high) subpopulation in A549 cells treated with TGF-β, which might explain its capability to induce metastatic progression. These results thus validate the existence of an evolutionary conserved TGF-β-inducible post-transcriptional regulon that controls EMT and subsequent metastatic progression of lung cancer.

MeSH terms

  • CD24 Antigen / metabolism
  • Cell Line, Tumor
  • Cytokines / genetics
  • Cytokines / metabolism*
  • Disease Progression
  • Epithelial-Mesenchymal Transition / genetics*
  • Gene Expression Regulation, Neoplastic
  • Heterogeneous-Nuclear Ribonucleoproteins / metabolism
  • Humans
  • Hyaluronan Receptors / metabolism
  • Lung Neoplasms / genetics
  • Lung Neoplasms / metabolism*
  • Lung Neoplasms / pathology
  • Neoplasm Metastasis / genetics
  • Neoplasm Metastasis / pathology
  • Neoplasm Proteins / genetics
  • Neoplasm Proteins / metabolism*
  • Protein Binding
  • Proto-Oncogene Proteins c-akt / metabolism
  • Transforming Growth Factor beta / genetics
  • Transforming Growth Factor beta / metabolism*

Substances

  • CD24 Antigen
  • CD24 protein, human
  • Cytokines
  • FAM3C protein, human
  • Heterogeneous-Nuclear Ribonucleoproteins
  • Hyaluronan Receptors
  • Neoplasm Proteins
  • PCBP1 protein, human
  • Transforming Growth Factor beta
  • AKT2 protein, human
  • Proto-Oncogene Proteins c-akt