FoxM1: at the crossroads of ageing and cancer

Forkhead transcription factors are intimately involved in the regulation of organismal development, cell differentiation and proliferation. Here we review the current knowledge of the role played by FoxM1 in these various processes. This particular member of the Forkhead family is broadly expressed in actively dividing cells and is crucial for cell cycle-dependent gene expression in the G2 phase of the cell cycle. FoxM1 plays a crucial role in insuring the fidelity of the cell division process, as inhibition of FoxM1 activity results in serious aberrancies during mitosis, such as frequent chromosome missegregation, defects in cytokinesis and overt aneuploidy. FoxM1 expression also appears to be tightly correlated with the proliferative rate of a cell. For example, FoxM1 is one of the most significantly down-regulated genes in prematurely aged human fibroblasts (Progeria syndrome), while elevated expression of FoxM1 is seen in most human carcinomas. These observations suggest that interference with FoxM1 activity may contribute to the increase in mitotic errors seen in human diseases such as cancer and early onset of ageing diseases. In this review, several aspects of FoxM1 function will be discussed, as well as their implication in tumorigenesis.