Send to

Choose Destination
Cell Death Differ. 2009 Mar;16(3):368-77. doi: 10.1038/cdd.2008.148. Epub 2008 Oct 10.

Tumour cell survival signalling by the ERK1/2 pathway.

Author information

Laboratory of Molecular Signalling, The Babraham Institute, Babraham Research Campus, Cambridge CB22 3AT, UK.


Several advances in recent years have focused increasing attention on the role of the RAF-MEK-ERK1/2 pathway in promoting cell survival. The demonstration that BRAF is a human oncogene mutated at high frequency in melanoma, thyroid and colon cancer has provided a pathophysiological context, whilst the description of potent and highly selective inhibitors of BRAF or MEK has allowed a more informed and rational intervention in both normal and tumour cells. In addition, separate studies have uncovered new mechanisms by which the ERK1/2 pathway can control the activity or abundance of members of the BCL-2 protein family to promote cell survival. It is now apparent that various oncogenes co-opt ERK1/2 signalling to de-regulate these BCL-2 proteins and this contributes to, and even underpins, survival signalling in some tumours. New oncogene-targeted therapies allow direct or indirect inhibition of ERK1/2 signalling and can cause quite striking tumour cell death. In other cases, inhibition of the ERK1/2 pathway may be more effective in combination with other conventional and novel therapeutics. Here, we review recent advances in our understanding of how the ERK1/2 pathway regulates BCL-2 proteins to promote survival, how this is de-regulated in tumour cells and the opportunities this might afford with the use of new targeted therapies.

[Indexed for MEDLINE]
Free full text

Supplemental Content

Full text links

Icon for Nature Publishing Group
Loading ...
Support Center