News Finding: The special environment of crypt tissue and the tendency of the cells with similar adhesion to aggregate will therefore discharge the mutated cell, hence maintaining the tissue homeostasis.
Paper Finding: Our results reveal a tumor suppressing function arising from the interactions between dynamic subcellular APC network and the adhesion gradient in the crypt, which promotes the elimination of mutant cells with high Wnt signaling.
News Context: Extensive mathematical simulation results show that the mutated cells with enhanced Wnt signaling acquire increased adhesion in comparison to the normal cells, which therefore move rapidly toward the upper part of the crypt and are discharged more easily. The special environment of crypt tissue and the tendency of the cells with similar adhesion to aggregate will therefore discharge the mutated cell, hence maintaining the tissue homeostasis. In vivo experiment with a mouse model confirms the simulation results that, in the case of abnormal crypt, the cells with high proliferation in fact move slower.
Paper Context: This observation suggests that the effects of mutations are modulated by a dynamic competition between tumor promoting and suppressive forces that may depend on the signaling status of individual cells and their local microenvironment. Our results reveal a tumor suppressing function arising from the interactions between dynamic subcellular APC network and the adhesion gradient in the crypt, which promotes the elimination of mutant cells with high Wnt signaling. Subversion of these interactions permits mutant cells to persist in the crypt and initiate CRC.