Loss of Function of E-Cadherin in Embryonic Stem Cells and the Relevance to Models of Tumorigenesis

Figure 6

Aberrant E-cadherin expression and neoplasm formation. (a) E-cadherin functions in epithelial cells to enable recognition and responsiveness to antiproliferative and proapoptotic signals (shown by green arrows and receptors) and repression of recognition and responsiveness to proproliferative and antiapoptotic signals (shown by red arrows). (b) Upon dysregulation of E-cadherin expression the epithelial cell circumvents antiproliferative and proapoptotic signal regulation and, instead, responds to proproliferative and antiapoptotic stimuli, if present (shown by red receptors on the cell). For simplicity, such a cell is referred to as a cancer stem cell (CSC). At this point the CSC may exhibit restoration of E-cadherin expression, re-establish within the epithelium and lose its stem cell-like phenotype (i.e., return to the state shown in (a)). (c) The CSC exhibits asymmetric self-renewal leading to formation of TACs which, due to dysregulation of E-cadherin, fail to participate in normal tissue formation and, instead, form a neoplasm. (d) The CSC and TACs may exhibit restoration of E-cadherin expression allowing their reestablishment within the epithelium, resulting in a neoplasm of latent tumorigenicity (NLT).