Interweaving the Cell Cycle Machinery with Cell Differentiation

A comprehensive understanding of the mechanisms coupling cell cycle exit and differentiation is important for both cancer biology and tissue development. Cancer cells can arise from either stem/progenitor cells that fail to exit the cell cycle and differentiate, or from de-differentiated cells that have re-entered the cell cycle. Much of our current understanding of this coupling is based on observations made in transformed cell lines. These studies have shown that enforcing proliferation prevents differentiation and inducing growth arrest leads to differentiation; thus, one widely-held view is that changes in cell cycle regulators simply induces cell cycle exit, a pre-requisite for differentiation. However, recent evidence indicates that cell cycle regulators can affect differentiation in other ways as well. They can have a role establishing the new transcriptional program that accompanies differentiation—in its most radical form, the molecular mechanism of arrest might even be an integral component of t...