Integrin Signaling, Cell Survival, and Anoikis: Distinctions, Differences, and Differentiation
Figure 4
Differentiation state-specific mechanisms of integrin 1/Fak/Src-mediated control of human intestinal epithelial cell survival and anoikis. In undifferentiated enterocytes (a), 1 integrin/Fak signaling recruits Src which acts as a cornerstone in the subsequent engagement of PI3-K/Akt-1 and MEK/Erk in the suppression of anoikis. However, in contrast to PI3-K/Akt-1, MEK/Erk is not required for survival due to its non-to-marginal roles in the regulation of the expression/functions of Bcl-2 homologs and its noninvolvement in suppressing the activation of the enterocyte undifferentiated state-selective apoptotic kinase isoform p38β. In differentiated enterocytes (b), MEK/Erk remains Src dependent but not PI3-K/Akt-1 (which however remains Fak-dependent). PI3-K/Akt-1 and MEK/Erk are now both required for survival, as they both play major roles in the regulation of Bcl-2 homolog expression/functions as well as in suppressing the activation of the enterocyte differentiated state-selective apoptotic kinase isoform p38δ. +, up-regulation of expression; −, down-regulation of expression.
