Fundamental aspects of the cell cycle and signal transduction

Abstract

During normal cycles of cell growth and division, cells are exquisitely sensitive to their environment, responding to many stimuli ranging from nutrient availability, growth factors, and cell density with either increased proliferation or growth arrest. The cell's ability to sense and respond to these environmental cues is lost on the progression of cells to a malignant state, rendering cancer cells resistant to growth inhibition by growth factor withdrawal, contact inhibition, or irradiation. These cancerous cells acquire many genetic and epigenetic mutations that can constitutively activate signaling pathways to mimic growth factor signaling, block growth inhibitory signals, and fundamentally alter core components of the cell-cycle machinery, removing key inhibitors or increasing amounts and activity of key activators. Although the genetic alterations of many upstream genes of diverse function have been shown to lead to malignancy, in the end these upstream factors feed into a core network that governs cell-cycle progression. © 2006 Springer Science+Business Media, Inc.