Figure 1.

Tumorigenic functions of Par3 in skin and breast cancer. (a) Par3 has both oncogenic and tumour-suppressive functions in the skin. Loss of Par3 reduces papilloma induced by H-Ras and TPA (12-O-tetradecanoylphorbol-13-acetate) in mouse skin. Alternatively, loss of Par3 promotes formation of the highly aggressive keratoacanthomas. (b,c) In breast, loss of Par3 promotes invasion and metastasis. Loss of Par3 mislocalizes aPKC and cooperates with oncogenic Notch intracellular domain (NICD) to activate Jak/Stat signalling and induction of matrix metalloproteinases to degrade the extracellular matrix, and enable invasion and metastasis (b). Loss of Par3 can also delocalize the Rac-GEF Tiam to hyperactivate Rac1, which can cooperate with ErbB2 to promote invasion by altering cell–cell adhesions (c). (Online version in colour.)