Article Text

Download PDFPDF

Journal club
A novel mechanism for MET and EGFR axis regulation in non-small cell lung cancer involving microRNA-27a and Sprouty2
  1. Omair Shariq
  1. Correspondence to Dr Omair Shariq, Department of Surgery, Chelsea and Westminster Hospital NHS Trust, 369 Fulham Road, London SW10 9NH, UK; omair.shariq{at}

Statistics from

Request Permissions

If you wish to reuse any or all of this article please use the link below which will take you to the Copyright Clearance Center’s RightsLink service. You will be able to get a quick price and instant permission to reuse the content in many different ways.

Epidermal growth factor receptor (EGFR) and hepatocyte growth factor receptor (MET) are tyrosine kinase receptors that have been implicated in the pathogenesis of non-small cell lung cancer (NSLC). Sprouty2, a ubiquitously expressed protein, has been shown to upregulate EGFR and MET in several types of cancers. Conversely, microRNAs are small non-coding RNA molecules that regulate gene expression negatively, and microRNA-27a (miR-27a) is thought to function as a tumour suppressor in NSLC. However, the regulatory pathways between MET, EGFR, Sprouty2 and miR-27a have not been fully elucidated in lung cancer.

Using gene expression analysis in A549 lung cancer cells, Acunzo et al 1 show that miR-27a overexpression results in reduced levels of EGFR and MET. In addition, they found that overexpression of miR-27a caused a reduction of Sprouty2 levels in the same cell line.

To investigate the relationship between Sprouty2, EGFR and MET, RNA interference was used to silence Sprouty2. This resulted in a downregulation of both MET and EGFR levels. Finally, the authors demonstrated that, in cells with a combination of both miR-27a overexpression and Sprouty2 silencing, downregulation of EGFR and MET was greater than when miR-27a was not overexpressed.

From these findings, Acunzo et al propose that miR-27a downregulates MET and EGFR via two different pathways: (1) directly by negatively regulating gene expression; and (2) indirectly through Sprouty2 downregulation. This study suggests a novel mechanism through which the EGFR and MET signalling pathways are regulated in NSLC and may provide a unique strategy for targeted lung cancer therapies in the future.

  • ▸ Acunzo M, Romano G, Palmieri D, et al. Cross-talk between MET and EGFR in non-small cell lung cancer involves miR-27a and Sprouty2. Proc Natl Acad Sci USA 2013;110:8573–8.


View Abstract


  • Competing interests None.

  • Provenance and peer review Not commissioned; internally peer reviewed.