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. Author manuscript; available in PMC: 2019 Jul 29.
Published in final edited form as: J Pathol. 2014 Feb;232(3):283–288. doi: 10.1002/path.4298

Figure 1.

Figure 1

Loss of key tumour suppressor genes in CAFs promotes tumour cell progression to malignancy. Loss of RB in normal and carcinoma-associated fibroblasts promotes proliferation, inhibits differentiation and increases invasion through collagen of co-cultured keratinocytes and tumour epithelia [32,36]. The effect of RB loss in fibroblasts was dependent on production of keratinocyte growth factor (KGF) that acted on co-cultured epithelial cells to promote growth through the KGF receptor (FGFR2b) and signalling through AKT to Ets-2 and its target genes, such as MMPs. Similarly, loss of PTEN in CAFs promoted production of MMPs and chemokines through deregulation of Ets-2, achieved in part through phosphorylation of Ets-2 by Akt and also via loss of PTEN-induced repression of miR-320 that targets Ets-2.