Figure 5.

Proposed model of breast tumour-mediated regulation of CCN2 and type I collagen in neighbouring fibroblasts in the tumour microenvironment. While fibroblasts in the normal stroma maintain the structure and function of the ECM, direct contact of tumour-associated fibroblasts with breast tumour cells in the tumour microenvironment leads to degradation of the ECM and/or fibrosis. We hypothesise that this is caused by increased expression of Smad7 that downstream negatively affects the expression of CCN2 and type I collagen, partly through inactivation of the MEK/ERK signalling pathway (illustration by I. Jastram).