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Cell migration

The importance of being selective

Nature Reviews Molecular Cell Biology volume 9, pages 426–427 (2008)Cite this article

This selectivity makes p110α a tempting drug target for the inhibition of tumour angiogenesis.

Ubiquitous knockout of p110α causes angiogenesis defects at mid-gestation. However, it is unclear whether this defect is due to the loss of p110α or due to the resulting upregulation of p85, which has dominant-negative effects on all p110 isoforms. To selectively investigate the role of p110α activity in angiogenesis, the authors devised two genetic approaches: they replaced endogenous p110α with a kinase-dead allele without altering the expression of p110α and p85, and they inactivated p110α in endothelial cells using Cre/loxP-mediated recombination. Ubiquitous or endothelial cell-specific inactivation of p110α led to severe defects in angiogenic sprouting and vascular remodelling and resulted in embryonic lethality. How does p110α exert this crucial endothelial cell-autonomous function?

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References

ORIGINAL RESEARCH PAPER

  1. Graupera, M. et al. Angiogenesis selectively requires the p110α isoform of PI3K to control endothelial cell migration. Nature 30 April 2008 (doi:10.1038/nature06892)

FURTHER READING

  1. Adams, R. H. & Alitalo, K. Molecular regulation of angiogenesis and lymphangiogenesis. Nature Rev. Mol. Cell Biol. 8, 464–478 (2007)

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Authors
  1. Ekat Kritikou
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Kritikou, E. The importance of being selective. Nat Rev Mol Cell Biol 9, 426–427 (2008). https://doi.org/10.1038/nrm2422

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