Fig. 3

Dynamic hierarchy and phenotypic plasticity of CSCs are prerequisites for CRLM. The intestinal crypt-villus structure is a dynamic stem cell hierarchical organization essential in colorectal cancer progression and metastasis. The compartment of hierarchical organization of colorectal cancer contains tumor cells in different states: SC cells, TA cells, and TD cells. Stem cells (SC) at the apex of hierarchies generate transient amplifying (TA) progenitor cells, and TA cells differentiate into terminally differentiated (TD) cells. B and C represent the hardwired stem cell hierarchy and the novel dynamic stem cell hierarchy, respectively. The latter model has a more plastic stem cell hierarchy, meaning that TA and TD cells can dedifferentiate to replace lost SCs through reprogramming. D. The role of cellular plasticity in colorectal cancer metastasis. CRC models demonstrate that Lgr5 + CSCs initiate and maintain metastasis, but tumor cells that escape the primary tumor and disseminated cells found in the blood circulation are overwhelmingly Lgr5- cells. Lgr5- cells were seeded in the metastatic site, and Lgr5 + cells appeared in the metastatic site after development period. When Lgr5 + cells are lost, Lgr5- cells replenish the eliminated Lgr5 + cells by dedifferentiation