Growth factors are required to initiate the G1 phase of the cell cycle. One well-studied growth factor is the epidermal growth factor (EGF).
The signaling cascade starts with the EGF ligand binding to its cell-surface receptor, known as the epidermal growth factor receptor (EGFR). This binding stimulates receptor dimerization and subsequent activation.
EGFR activation triggers the sequential activation of a cascade of components downstream. These include Ras, Raf, MEK, and ERK, all of which are known as oncogenes. Oncogenes are genes capable of transforming healthy cells into cancerous cells. The transition from normal cells to cancerous cells is a complex process of genetic alterations involving multiple factors from networks of signaling pathways. Of these, oncogenes such as Ras, Raf, MEK, and ERK play an essential role.
Under normal circumstances, however, these genes play essential roles in regulating cellular processes, including cell proliferation, differentiation, motility, and apoptosis. The difference between oncogenes under normal versus cancerous conditions is that in the latter situation, signals stemming from these oncogenes become dysregulated, such as the signal for growth becoming active all the time.
Not surprisingly, these four oncogenes are all found to be at significantly elevated levels in a number of cancer types.
As shown in Figure 3 below, activated ERK translocates to the cell nucleus, where it promotes transcriptional activation of a plethora of genes with diverse cellular functions, including cell proliferation, cell differentiation, programmed cell death (also called apoptosis), and motility.
