Quantitative proteomic analysis of sphere-forming stem-like oral cancer cells

Abstract

Insights

Oral cancer stem-like cells (CSCs) were enriched from a highly invasive cell line. Proteomic analysis revealed significant alterations in pathways, with CREB-binding protein (CBP) and phosphorylated CREB-1 over-expressed in CSCs.

Area of Science:

  • Oncology
  • Proteomics
  • Cancer Stem Cell Biology

Background:

  • Oral squamous cell carcinoma (OSCC) progression is linked to cancer stem-like cells (CSCs).
  • Understanding the proteomic landscape of OSCC CSCs is crucial for identifying therapeutic targets.

Purpose of the Study:

  • To identify target proteins in oral cancer stem-like cells (CSCs) using mass spectrometry-based quantitative proteomics.
  • To characterize proteomic differences between CSC-like and non-CSC oral cancer cells.

Main Methods:

  • Enrichment of CSCs using sphere-formation assays in UM1 (highly invasive) and UM2 (lowly invasive) tongue SCC cell lines.
  • Quantitative proteomic analysis of CSC-like and non-CSC UM1 cells via tandem mass tagging and Orbitrap mass spectrometry.

Main Results:

  • CSCs were enriched in UM1 but not UM2 cell lines.
  • Stem cell markers (SOX2, OCT4, SOX9, CD44) were upregulated; HIF-1 alpha and PGK-1 were downregulated in CSC-like UM1 cells.
  • Differential protein expression observed in cell cycle, metabolism, signaling, and RNA splicing pathways; CREB-binding protein (CBP) and phosphorylated CREB-1 were significantly overexpressed in CSC-like UM1 cells.

Conclusions:

  • CSCs can be enriched from highly invasive UM1 oral cancer cells.
  • Significant proteomic alterations distinguish CSC-like from non-CSC UM1 cells.
  • Upregulation of CBP and phosphorylated CREB-1 suggests activation of the CREB pathway in oral CSCs.

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