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. Author manuscript; available in PMC: 2014 Jan 8.
Published in final edited form as: J Mammary Gland Biol Neoplasia. 2011 Aug 7;16(3):10.1007/s10911-011-9226-0. doi: 10.1007/s10911-011-9226-0

Figure 3.

Figure 3

Integrin-mediated signaling pathways regulate normal epithelial polarity and differentiation. Adhesion of α6β4 integrin to the basal lamina (B. Lamina) results in activation of FAK, and subsequent signaling to Rac to promote cell proliferation and survival via p21 and NFkB. Signaling through Rac to promote basal secretion of laminin-5 (LN-5) helps establish cell polarity. Adhesion to the basal lamina prevents apoptosis via PAK activation of Bcl2 and Bad. Loss of adhesion to the basal lamina results in apoptosis, necessary for luminal clearing. In the case of tumorigenesis, tumor cells degrade the basal lamina, and invade into the stromal matrix. Tumor cells can secrete their own autocrine LN-5 and prevent apoptosis. Moreover, α2β1 integrin adhesion to collagen promotes cell proliferation and survival via activation of FAK, pERK, and PI-3-K pathways. Activated pFAK antagonizes p53 to prevent apoptosis.