Figure 7. Scheme of p53-CD44-p53 Axis in Untransformed and Transformed Cells.

(A) The p63 protein expression was inhibited by two independent shRNAs in pLKO1-Puro lentiviral vector in BPEC-T cells. The cells were lysed and analyzed for p63 and CD44 protein expression by western blotting one week after infection with viral shRNA constructs.

(B) The scheme of the function of p53-CD44-p53 axis in immortalized BPEC-T cells. Unknown signals, dependent on a cell’s position within an epithelial cell cluster, trigger induction of p53 expression, which leads, in turn, to CD44 repression, slower proliferation and increased apoptosis in response to a strong genotoxic stress. Conversely, increased CD44 expression can inhibit p53 stability by stimulating Her2-dependent activation of MDM2 protein expression (Mayo and Donner, 2001; Zhou et al., 2001).

(C) The summary of CD44 function in tumor cells. In highly tumorigenic BPLER cells with SV40 LTg-inactivated p53, CD44 is essential for anchorage-independent growth, tumor growth kinetics as well as tumor-initiating ability. In A549 cells, suppression of p53 expression accelerates tumor growth, which is dependent on elevated CD44 expression resulting from its derepression occuring in the absence of p53. The expression of CD44 is positively regulated by p63 in BPEC-T cells, in BPLER cells and in A549 cells, but the detailed molecular mechanism of this regulation in not known.