Neuro-mimetic reprogramming and epigenetic unlocking drive lung cancer stem cell adaptation to the brain microenvironment

Brain contact reprograms lung cancer stem cells in an intracranial in vivo model, producing neuro-mimetic adaptation marked by epigenetic unlocking and Nestin hyperphosphorylation at S957 and S963.

• Why it matters: It addresses whether CSCs exposed to brain parenchyma terminally differentiate or instead undergo adaptive plasticity that enables lethal brain metastasis.
• What they did: Lung-derived CSCs were injected intracranially and analyzed with quantitative total proteomics and phosphoproteomics, including kinase substrate enrichment and inhibitor-based functional validation.
• The result: The brain niche desensitizes the systemic metastatic program while upregulating Ngfr, Fabp7, Pbx3, Vgf, and S100b, downregulating Dnmt3a, excluding Id1, and activating Prkcq and Map3k7 to create tissue-specific adaptive liabilities.

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