Cross-talk between MET and EGFR in non-small cell lung cancer involves miR-27a and Sprouty2

Proc Natl Acad Sci U S A. 2013 May 21;110(21):8573-8. doi: 10.1073/pnas.1302107110. Epub 2013 May 6.

Abstract

In the past decade, we have observed exciting advances in lung cancer therapy, including the development of targeted therapies. However, additional strategies for early detection and tumor-based therapy are still essential in improving patient outcomes. EGF receptor (EGFR) and MET (the receptor tyrosine kinase for hepatocyte growth factors) are cell-surface tyrosine kinase receptors that have been implicated in diverse cellular processes and as regulators of several microRNAs (miRNAs), thus contributing to tumor progression. Here, we demonstrate a biological link between EGFR, MET, and the miRNA cluster 23a ~ 27a ~ 24-2. We show that miR-27a regulates MET, EGFR, and Sprouty2 in lung cancer. In addition, we identify both direct and indirect mechanisms by which miR-27a can regulate both MET and EGFR. Thus, we propose a mechanism for MET and EGFR axis regulation that may lead to the development of therapeutics in lung cancer.

Keywords: cell signaling; epigenetics.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Carcinoma, Non-Small-Cell Lung / genetics
  • Carcinoma, Non-Small-Cell Lung / metabolism*
  • Carcinoma, Non-Small-Cell Lung / pathology
  • Cell Line, Tumor
  • ErbB Receptors / biosynthesis*
  • ErbB Receptors / genetics
  • Gene Expression Regulation, Neoplastic*
  • Humans
  • Intracellular Signaling Peptides and Proteins / biosynthesis*
  • Intracellular Signaling Peptides and Proteins / genetics
  • Lung Neoplasms / genetics
  • Lung Neoplasms / metabolism*
  • Lung Neoplasms / pathology
  • Membrane Proteins
  • MicroRNAs / genetics
  • MicroRNAs / metabolism*
  • Proto-Oncogene Proteins c-met / biosynthesis*
  • Proto-Oncogene Proteins c-met / genetics
  • RNA, Neoplasm / genetics
  • RNA, Neoplasm / metabolism*

Substances

  • Intracellular Signaling Peptides and Proteins
  • MIRN27 microRNA, human
  • Membrane Proteins
  • MicroRNAs
  • RNA, Neoplasm
  • SPRY2 protein, human
  • EGFR protein, human
  • ErbB Receptors
  • MET protein, human
  • Proto-Oncogene Proteins c-met