Mapping Phosphorylation in Cancer

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Phosphorylation is a key mechanism for regulation of protein activity and the phosphorylation of tyrosine residues, in particular, is important in signalling pathways. Aberrant phosphorylation has been observed in many cancers and has driven the development of kinase inhibitors that have utility in a number of cancer subtypes. Since abnormal activation of signalling pathways is a common feature that accompanies tumour initiation and progression, methods to assess signalling pathway status of cancer tissue relative to normal could provide important insights.

A group of US researchers has now conducted a detailed analysis of tyrosine phosphorylation states in lung cancer compared to normal tissue. The work documents a large set of sites that are differentially phosphorylated in the cancer tissue, immediately providing a number of drug target candidates. Taking the study a step further, the group has developed computational methodology to identify signalling pathways where phosphorylation activity is strongly correlated with the lung cancer phenotype.

The EGFR signalling pathway. Pink indicates higher phosphorylation in tumour samples, while green indicates higher phosphorylation in normal tissue samples. Full details can be found in PLoSone.

The EGFR signalling pathway. Pink indicates higher phosphorylation in tumour samples, while green indicates higher phosphorylation in normal tissue samples. Full details can be found in PLoSone.

The results provide a highly predictive set of signatures that reliably distinguish each lung cancer from normal. Since the signatures identify proteins and pathways where phosphorylation should be inhibited, the methodology highlights potential new targets for drug discovery.

The study is published in the journal PLoSone.


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