Figure 1.

Illustrative example of a signal transduction network relevant to a cancer hallmark phenotype, uncontrolled proliferation. In the normal context cell proliferation is driven by growth factors that bind to receptor tyrosine kinases (RTKs); yet it can also be an outcome of alterations in signal transduction proteins. In panel A, the six subgraphs that are typically referred to as separate pathways in the biological literature are colored differently. Panels B–D indicate select outcomes of a discrete dynamic model of this network, whose regulatory functions are indicated in the bottom of panel B. The unperturbed system (B) has two possible steady states, a non-proliferative one and one with controlled proliferation (Proliferation = 1), among which it may select depending on environmental signals. (C) Alterations in certain oncogenes or tumor suppressor genes yield a single outcome: uncontrolled proliferation (Proliferation = 2). (D) Targeted inhibition of an oncogene (here, PI3K) may not eliminate the proliferating phenotype. Further details are provided in Box 1.