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Disruption of WNT/Notch signaling in pancreatic cancer reveals tumors depend on the intricate equilibrium of malignant cell states - PubMed

4 hours ago
  • #Pancreatic cancer
  • #WNT/Notch signaling
  • #Tumor heterogeneity
  • Disruption of WNT/Notch signaling in pancreatic cancer affects tumor growth and metastasis.
  • Pancreatic ductal adenocarcinoma (PDAC) organizes in a pattern where WNT-responding cells (WNT-R) neighbor WNT-secreting cells (WNT-S).
  • The WNT-R state is transient and gives rise to a stable WNT-S state.
  • A subset of WNT-S cells expressing DLL1 forms a functional niche for WNT-R cells.
  • Genetic inactivation of WNT secretion or Notch pathway components disrupts PDAC tissue organization.
  • Human PDAC tissues show conservation of these cell populations.
  • PDAC growth depends on an equilibrium of distinct cancer cell states.
  • The study reveals principles of solid tumor organization and potential therapeutic opportunities.