A change of state leads to rewiring

McCarthy, Nicola

doi:10.1038/nrc3662

In Brief
Published: 23 December 2013

Signalling

A change of state leads to rewiring

Nicola McCarthy

Nature Reviews Cancer volume 14, page 6 (2014)Cite this article

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Epithelial tumour cells are known to undergo a form of epithelial to mesenchymal transition (EMT) during the course of tumour progression, and mesenchymal markers are associated with poor prognosis and drug resistance. How molecular signalling pathways are 'rewired' in cells that have undergone EMT is not well characterized. Frank McCormick and colleagues used non-small-cell lung cancer cells expressing regulatable transcription factors that induce EMT to investigate the effects of EMT on signalling pathways downstream of receptor tyrosine kinases. They found that EMT is associated with reduced expression of ERBB3 and reduced rates of proliferation in serum-free conditions owing to reduced PI3K activation. Re-expression of ERBB3, activation of PIK3CA (a catalytic subunit of PI3K) or growth factor stimulation rescued PI3K signalling in the absence of serum. Importantly, examination of mesenchymal-like tumours in vivo showed that PIK3CA upregulation occurs in tumours with reduced ERBB3 expression.

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References

Salt, M. B., Bandyopadhyay, S. & McCormick, F. Epithelial to mesenchymal transition rewires the molecular path to PI3-kinase-dependent proliferation. Cancer Discov. http://dx.doi.org/10.1158/2159-8290.CD-13-0520 (2013)

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