Despite mounting evidence for the role of the tumour microenvironment (TME) in affecting surrounding cells and its involvement in metastatic progression, little is known about how stromal cells can influence the behaviour of cancer epithelial cells and how they affect their response to target therapy. Under normal physiological conditions, the stroma serves as a barrier to epithelial cell transformation, while the interplay between epithelial cells and the microenvironment can maintain epithelial polarity and modulate growth inhibition.