Stem cell control in the lung by an autocrine injury-activated Igf complex
Summary
Stem cells proliferate after injury to repair damaged tissue, and chronic injury can promote cancer. However, the injury-activated signals and regulatory mechanisms, and their relationship to cancer, are poorly understood. Here, we identified insulin-like growth factor 2 (Igf2) as an injury-activated mitogen for lung neuroendocrine stem cells, which are facultative airway progenitors and a cell of origin of small-cell lung cancer in mice. Igf2 was constitutively produced by the stem cells
Content
# Stem cell control in the lung by an autocrine injury-activated Igf complex
*Published: 2026 Apr 16*
Stem cells proliferate after injury to repair damaged tissue, and chronic injury
can promote cancer. However, the injury-activated signals and regulatory
mechanisms, and their relationship to cancer, are poorly understood. Here, we
identified insulin-like growth factor 2 (Igf2) as an injury-activated mitogen
for lung neuroendocrine stem cells, which are facultative airway progenitors and
a cell of origin of small-cell lung cancer in mice. Igf2 was constitutively
produced by the stem cells but sequestered in the niche by coexpressed Igf
binding proteins (Igfbps). Airway injury released Igf2 and induced proliferation
by transiently activating Igf2 receptors and repressing retinoblastoma (Rb)
tumor suppressor. Permanent pathway activation by Rb deletion initiated
continuous stem cell division. Thus, beyond their classical hormonal roles in
physiology, growth, and aging, Igf proteins operate locally and rapidly with
Igfbp and Rb to control injury-induced stem cell proliferation and tumor
initiation.
DOI: 10.1126/science.adt1310