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. 2010 Nov 9;103(11):1716–1723. doi: 10.1038/sj.bjc.6605975

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Copyright © 2010 Cancer Research UK

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Loss of Dab2 facilitates EMT. In the basal state, cytosolic Grb2 can be found in association with Dab2 or Sos. Loss of Dab2 expression, commonly observed in breast cancer, is postulated to increase the proportion of Grb2 associated with Sos, resulting in Ras activation (RAS^*), stimulation of MAPK signalling and phosphorylation of ERK (pERK). Activation of ERK stimulates increased transcription of the TGFβ isoforms, in particular the TGFβ2 isoform. Increased TGFβ stimulation induces transient EMT, and also initiates establishment of an autocrine TGFβ signalling loop leading to a stable EMT phenotype exemplified by increased expression of EMT markers. Inhibition of TGFβ signalling with SB431542 or MAPK signalling with U0126 decreases TGFβ production and causes partial reversion of the EMT phenotype.