Phenotypic plasticity and epithelial-mesenchymal transitions in cancer and normal stem cells?

Abstract

Cancer stem cells (CSCs) are similar to normal stem cells in their ability to self-renew and to generate large populations of more differentiated descendants. In contrast to the hierarchical organization that is presumed to be the prevalent mode of normal tissue homeostasis, phenotypic plasticity allows cancer cells to dynamically enter into and exit from stem-cell states. The epithelial-mesenchymal transition (EMT) has been closely associated with the acquisition of both invasive and stem-cell properties in cancer cells. Thereby, EMT programs emerge as important regulators of phenotypic plasticity in cancer cells including their entrance into stem-cell states. Much is still to be learned about the regulation of EMTs through epigenetic mechanisms in cancer cells and the contributions that EMT programs make to normal tissue homeostasis.

Figure 1. Multi-step progression of cancer and the cancer stem cell (CSC) model

Adapted from Weinberg RA., “The Biology of Cancer”, Garland Science. (a) Normal stem cells (SCs) acquire an initial mutation and evolve into a mutant SC population (cells of different cellular states are depicted as circles, mutational events are indicated by pink halo; cells carrying a specific mutations are indicated by colored quarter within “cells”); the latter continues to generate, more differentiated descendants carrying that mutation. Cells within the initially formed mutant SC population acquire another mutation and evolve into an incrementally more neoplastic SC population. The end product is a CSC with tumor-initiating potential. (b) The mutations driving multi-step tumor progression do not strike various SC populations, as indicated above, but strike transit-amplifying populations that are introduced into the corresponding SC populations via a dedifferentiation process.