Figure 7

Two possible mechanisms by which myofibroblasts acquire anoikis resistance via integrin receptors for laminin-332 during tissue remodeling. Direct and indirect interactions may occur between invasive tumor cells and myofibroblasts in the interface zone of invasive ductal carcinoma. Myofibroblasts within the interface zone could be stimulated to express laminin-332 by diffusible factors from invasive breast cancer cells. Binding of laminin-332 to integrin α3β1 on the myofibroblasts turns on a cell-survival signaling pathway mediated by Akt phosphorylation. In this case, myofibroblasts may simultaneously use synoikis to overcome anoikis. In addition, in the border between the tumor zone and the interface zone, invasive breast cancer cells can directly interact with myofibroblasts, leading to integrin β4 neoexpression. Once integrin β4 is induced, myofibroblasts use both integrin α3β1 and α6β4 as receptors for laminin-332, and become resistant to anoikis via Akt phosphorylation (laminin-332 dependent) and Rac1 activation (laminin-332 independent). Moreover, integrin β4 neoexpression may inhibit myofibroblast aggregation through downregulation of β-catenin.