Expression and significance of notch signaling pathway in salivary adenoid cystic carcinoma

Ann Diagn Pathol. 2014 Feb;18(1):10-3. doi: 10.1016/j.anndiagpath.2013.10.001. Epub 2013 Oct 10.

Abstract

Notch signaling plays a role in stem cell biology, tumor formation, angiogenesis, and cell death. Targeting Notch pathway could serve as a therapeutic strategy in cancer. Little is known about the differential role of various components of the Notch pathway in salivary adenoid cystic carcinoma (AdCC). To investigate the association of the Notch pathway in AdCC carcinogenesis, we analyzed the Notch receptor (Notch-1, Notch-2, Notch-4) and Notch ligand (Jagged-1, Delta) expressions. The results showed elevated expression levels of all 5 proteins in AdCC tissue relative to normal salivary gland tissues. Jagged-1/Notch-2 coexpression was significantly associated with increased patient survival rate. The elevated expression level of these Notch receptors and ligands in AdCC points to Notch signaling as a key player in AdCC pathogenesis. Our data provide evidence for a relationship between Jagged-1/Notch-2 coexpression and better overall patient survival with AdCC. Targeting Notch signaling pathway may provide therapeutic benefits for these patients.

Keywords: AdCC; Adenoid cystic; CSC; Cancer stem cells; Carcinoma; Notch; Notch-2/Jagged-1; Targeted therapy; adenoid cystic carcinoma; cancer stem cells.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Aged, 80 and over
  • Biomarkers, Tumor / analysis
  • Calcium-Binding Proteins / analysis
  • Calcium-Binding Proteins / biosynthesis*
  • Carcinoma, Adenoid Cystic / metabolism*
  • Carcinoma, Adenoid Cystic / mortality
  • Female
  • Humans
  • Immunohistochemistry
  • Intercellular Signaling Peptides and Proteins / analysis
  • Intercellular Signaling Peptides and Proteins / biosynthesis*
  • Intracellular Signaling Peptides and Proteins / analysis
  • Intracellular Signaling Peptides and Proteins / biosynthesis*
  • Jagged-1 Protein
  • Kaplan-Meier Estimate
  • Male
  • Membrane Proteins / analysis
  • Membrane Proteins / biosynthesis*
  • Middle Aged
  • Receptors, Notch / analysis
  • Receptors, Notch / biosynthesis*
  • Salivary Gland Neoplasms / metabolism*
  • Salivary Gland Neoplasms / mortality
  • Serrate-Jagged Proteins
  • Signal Transduction* / physiology
  • Young Adult

Substances

  • Biomarkers, Tumor
  • Calcium-Binding Proteins
  • Intercellular Signaling Peptides and Proteins
  • Intracellular Signaling Peptides and Proteins
  • JAG1 protein, human
  • Jagged-1 Protein
  • Membrane Proteins
  • Receptors, Notch
  • Serrate-Jagged Proteins
  • delta protein