Figure 2. Epithelial stress response is associated with loss of polarity and repositioning of cell surface receptors.

Epithelial cells are polarized with the separation of the apical and basolateral membranes by specialized tight junctions between neighbouring cells. In contrast to apical positioning of the transmembrane mucins, certain other cell surface molecules, for example the receptor tyrosine kinases (RTKs), are restricted to the basolateral membranes. In the presence of inflammation and other settings that induce damage, there is loss of tight junction integrity and cell polarity. In turn, the transmembrane mucins are repositioned over the entire cell membrane and interact with RTKs. Loss of polarity allows epithelial cells to activate a programme of repair and survival²². Whereas the epithelial stress response is reversible and polarity is re-established after repair, loss of polarity is irreversible in carcinoma cells. Therefore, mucin 1 (MUC1) constitutively interacts with diverse RTKs and promotes their downstream signals, thus providing a mechanism by which carcinoma cells can exploit a physiological stress response for their own growth and survival.