Signal transduction in cancer

Abstract

Cancer is driven by genetic and epigenetic alterations that allow cells to overproliferate and escape mechanisms that normally control their survival and migration. Many of these alterations map to signaling pathways that control cell growth and division, cell death, cell fate, and cell motility, and can be placed in the context of distortions of wider signaling networks that fuel cancer progression, such as changes in the tumor microenvironment, angiogenesis, and inflammation. Mutations that convert cellular proto-oncogenes to oncogenes can cause hyperactivation of these signaling pathways, whereas inactivation of tumor suppressors eliminates critical negative regulators of signaling. An examination of the PI3K-Akt and Ras-ERK pathways illustrates how such alterations dysregulate signaling in cancer and produce many of the characteristic features of tumor cells.

Figure 1.

Cancer progression.

Figure 2.

The Ras-ERK and PI3K pathways.

Figure 3.

Regulation of cell proliferation by the Ras-ERK and PI3K-Akt pathways.

Figure 4.

Regulation of cell death by Ras-ERK and PI3K-Akt pathways.

Figure 5.

Regulation of metabolism by Ras-ERK and PI3K-Akt signaling. IDH*, mutated IDH.

Figure 6.

Cancer signaling networks. The figure illustrates the wide variety of intra- and intercellular signals affected in cancer, focusing on Ras-ERK and PI3K-Akt signaling. It is by no means comprehensive; many more pathways are involved and there are other stromal cells involved in paracrine signaling. Oncoproteins are indicated with yellow highlighting; tumor suppressors are indicated with dashed outlines. Arrows do not necessarily indicate direct interactions in this figure.