The decision to divide asymmetrically or symmetrically may be the major fundamental intrinsic difference between normal stem and cancer stem cells. The decision to utilize either CBP/catenin or p300/catenin driven transcription, i.e. to divide symmetrically or asymmetrically, appears to be an extremely fundamental event as it is already critical even at the 8-cell stage of embryogenesis. The ultimate decision for a cell to retain potency or initiate differentiation is dependent upon numerous inputs including the activation of different growth factors, cytokines, and hormones and the subsequent activation of different signal transduction complexes and kinase cascades, nutrient levels, oxygen levels, genetic mutations, adhesion to substratum. In the end these multiple pathways must be integrated and funneled down into a simple decision point, i.e., a yes/no binary decision. While it is known how to pharmacologically manipulate the balance of differential catenin coactivator usage (i.e., catenin/CBP versus catenin/p300) in stem/progenitor cell populations, understanding how a cell reads the enormously complex array of information from its environment to arrive at an eventual 0/1 binary decision remains to be understood.
USPTO Backgrounds
USPTO Backgrounds