Stem cell control and cancer initiation by an autocrine, injury-activated Igf complex
Abstract
Stem cells rapidly proliferate after injury to repair damaged tissue, and chronic injury predisposes to cancer. However, injury-activated mitogens, the mechanisms that keep them inactive until injury, and their role in cancer are not understood. Here we identify Igf2 as the injury-activated mitogen for neuroendocrine stem cells, a facultative airway stem cell and origin of small cell lung cancer. Igf2 is constitutively produced by the stem cells but sequestered in inactive form by co-expressed Igf binding proteins. Injury releases Igf2 and induces proliferation by activating its receptors and repressing Rb tumor suppressor, which normally enforces stem cell quiescence. Persistent pathway activation initiates oncogenesis. Thus, in addition to its classical hormonal roles in physiology, growth, and aging, Igf operates locally with Igf binding proteins and Rb to control injury-induced stem cell activation and cancer. This pathway may also control related stem cells and cancers of the body and brain.
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Research summary
The paper claims that injury-activated Igf2 promotes neuroendocrine stem cell proliferation and initiates oncogenesis by repressing the Rb tumor suppressor. This research is relevant as it explores the mechanisms of stem cell activation and cancer initiation, which are linked to aging processes and may provide insights into the root causes of age-related diseases.
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