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Vitamin D Binding Protein, a Ligand of Integrin beta 1, Motivates Both Tumor Cells and Schwann Cells to Promote Perineural Invasion in Pancreatic Ductal Adenocarcinoma

  • 0State Key Laboratory of Systems Medicine for Cancer, Shanghai Cancer Institute, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, 200240, P. R. China.
Advanced Science (weinheim, Baden-Wurttemberg, Germany) +

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September 9, 2025

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September 9, 2025

View abstract on PubMed

Summary

This summary is machine-generated.

Group-specific component protein (GC) drives pancreatic cancer nerve invasion by activating Schwann cells via integrin signaling. Targeting this pathway reduces pancreatic ductal adenocarcinoma progression and recurrence.

Area Of Science

  • Oncology
  • Molecular Biology
  • Cancer Research

Background

  • Perineural invasion (PNI) is a hallmark of pancreatic ductal adenocarcinoma (PDAC), correlating with poor prognosis.
  • The underlying mechanisms of PNI in PDAC are not fully understood.

Purpose Of The Study

  • To elucidate the molecular mechanisms of PNI in pancreatic ductal adenocarcinoma.
  • To identify key molecular players involved in cancer-nerve interactions in PDAC.

Main Methods

  • Gene expression analysis to identify upregulated genes in PNI.
  • In vitro cell culture experiments (GC knockdown, cell invasiveness assays).
  • In vivo studies using KPC mice and orthotopic xenografts, ITGB1 blockade.
  • Clinical sample analysis correlating protein levels with PNI severity.

Main Results

  • Group-specific component protein (GC) is significantly upregulated in PDAC and promotes PNI.
  • GC enhances PDAC cell invasiveness and activates Schwann cells via a dedifferentiation program.
  • Integrin β1 (ITGB1) acts as the functional receptor for GC, mediating interactions between PDAC and Schwann cells.
  • Targeting the ITGB1-FAK pathway and GC silencing reduced PNI and tumor progression in preclinical models.
  • Clinical data showed positive correlations between GC, ITGB1, p-FAK, and PNI severity.

Conclusions

  • GC protein is a key mediator of PNI in PDAC, acting through integrin receptor signaling.
  • GC and ITGB1 represent potential therapeutic targets for reducing PNI and improving outcomes in pancreatic cancer.

Keywords:

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