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Control of proliferation by oncogenes and tumor suppressors


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.

Aurelien Naldi

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