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Proteomics

A discovery strategy for novel cancer biomarkers

Nature Reviews Cancer volume 10, page 597 (2010)Cite this article

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Andersen and colleagues used immunoaffinity precipitation followed by mass spectrometry to identify differential serine–threonine phosphorylation events in stable isotope labelling by amino acids in cell culture (SILAC)-labelled, PTEN-null PC-3 prostatic cancer cells that were treated with inhibitors of PDK1, AKT or a dual inhibitor of PI3K and mTOR. This approach allowed the quantification of 375 phosphopeptides that were relevant to PI3K pathway signalling, of which 71 were drug inhibited and 11 were reduced by all 3 PI3K pathway inhibitors.

The authors identified 'PI3K pathway nodes', which were the phosphorylation targets that were the most reduced by drug treatment. For example, phosphorylation of the ribosomal protein RPS6 was the most strongly inhibited by all three drugs, and PRAS40 was the most reduced phosphopeptide by AKT and PI3K–mTOR inhibition. To define common signalling modules, the authors analysed the phosphoproteins that were affected by all three inhibitors, and found that the modules most commonly inhibited were related to cytoskeletal functions, such as cell polarity and cytoskeletal organization. Additional modules commonly downregulated by the PDK1 and AKT inhibitors were related to vesicle transport and protein translation. These findings were consistent with the known inhibitory effects of these drugs on cancer cell motility, migration and invasion.

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References

ORIGINAL RESEARCH PAPER

  1. Andersen, J. N. et al. Pathway-based identification of biomarkers for targeted therapeutics: personalized oncology with PI3K pathway inhibitors. Sci. Trans. Med. 2, 43ra55 (2010)

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FURTHER READING

  1. Kolch, W. & Pitt, A. Functional proteomics to dissect tyrosine kinase signalling pathways in cancer. Nature Rev. Cancer 10, 618–629 (2010).

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Authors
  1. Meera Swami
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Swami, M. A discovery strategy for novel cancer biomarkers. Nat Rev Cancer 10, 597 (2010). https://doi.org/10.1038/nrc2922

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