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Updated: Feb 13, 2026

Spatial and Temporal Control of Murine Melanoma Initiation from Mutant Melanocyte Stem Cells
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Stem cell control and cancer initiation by an autocrine, injury-activated Igf complex

Yue Zhang1,2, Youcef Ouadah1,3, Yin Liu1

  • 1Stanford University Department of Biochemistry, Stanford, CA 94305, USA.

Biorxiv : the Preprint Server for Biology
|February 12, 2026
PubMed

Insights

Injury activates Insulin-like Growth Factor 2 (IGF2) in airway stem cells, driving proliferation and initiating small cell lung cancer. This pathway involves IGF binding proteins and Rb, controlling stem cell activation and oncogenesis.

Area of Science:

  • Cell Biology
  • Cancer Research
  • Pulmonology

Background:

  • Stem cell proliferation after injury aids tissue repair but chronic injury can lead to cancer.
  • Mechanisms of injury-activated mitogens and their role in cancer initiation are not fully understood.

Purpose of the Study:

  • To identify the injury-activated mitogen for neuroendocrine stem cells.
  • To elucidate the role of this mitogen in small cell lung cancer (SCLC) development.

Main Methods:

  • Identification of Insulin-like Growth Factor 2 (IGF2) as the key mitogen.
  • Analysis of IGF2 sequestration by IGF binding proteins.
  • Investigation of the role of Rb tumor suppressor in regulating stem cell quiescence.

Main Results:

  • IGF2 is identified as the injury-activated mitogen for airway neuroendocrine stem cells.
  • Injury releases sequestered IGF2, activating proliferation via receptor signaling and Rb repression.
  • Persistent activation of this pathway leads to oncogenesis and SCLC initiation.

Conclusions:

  • IGF2, acting locally with IGF binding proteins and Rb, controls injury-induced stem cell activation and cancer.
  • This pathway is crucial for understanding and potentially targeting SCLC.
  • The findings suggest potential roles in other stem cell-related cancers.

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