Control of proliferation by oncogenes and tumor suppressors

Taxon: Mammal
Process: Cancer
Submitter: Aurelien Naldi

Supporting paper: G.T. Zañudo, Jorge and Steinway, Steven N. and Albert, Réka (2018). Discrete dynamic network modeling of oncogenic signaling: Mechanistic insights for personalized treatment of cancer. Current Opinion in Systems Biology. 10.1016/j.coisb.2018.02.002

Model file(s)	Description(s)
2018_zanudo_proliferation.zginml	GINsim file

Summary:
This model is an 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. Six separate pathways are typically pointed out in biological literature. This model includes all of these pathways in a single network. The unperturbed system 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. Alterations in certain oncogenes or tumor suppressor genes yield a single outcome: uncontrolled proliferation (Proliferation = 2). Targeted inhibition of an oncogene (here, PI3K) may not eliminate the proliferating phenotype.