Involvement of calprotectin (S100A8/A9) in molecular pathways associated with HNSCC

Ali Khammanivong, Brent S. Sorenson, Karen F Ross, Erin B Dickerson, Rifat Hasina, Mark W. Lingen, Mark C Herzberg

Research output: Contribution to journalArticle

14 Citations (Scopus)

Abstract

Calprotectin (S100A8/A9), a heterodimeric protein complex of calcium-binding proteins S100A8 and S100A9, plays key roles in cell cycle regulation and inflammation, with potential functions in squamous cell differentiation. While upregulated in many cancers, S100A8/A9 is downregulated in squamous cell carcinomas of the cervix, esophagus, and the head and neck (HNSCC). We previously reported that ectopic S100A8/A9 expression inhibits cell cycle progression in carcinoma cells. Here, we show that declining expression of S100A8/A9 in patients with HNSCC is associated with increased DNA methylation, less differentiated tumors, and reduced overall survival. Upon ectopic over-expression of S100A8/A9, the cancer phenotype of S100A8/A9-negative carcinoma cells was suppressed in vitro and tumor growth in vivo was significantly decreased. MMP1, INHBA, FST, LAMC2, CCL3, SULF1, and SLC16A1 were significantly upregulated in HNSCC but were downregulated by S100A8/A9 expression. Our findings strongly suggest that downregulation of S100A8/A9 through epigenetic mechanisms may contribute to increased proliferation, malignant transformation, and disease progression in HNSCC.

Original languageEnglish (US)
Pages (from-to)14029-14047
Number of pages19
JournalOncotarget
Volume7
Issue number12
DOIs
StatePublished - Mar 22 2016

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Leukocyte L1 Antigen Complex
Down-Regulation
Neoplasms
Cell Cycle
Carcinoma
Calcium-Binding Proteins
DNA Methylation
Epigenomics
Cervix Uteri
Esophagus
Disease Progression
Cell Differentiation
Squamous Cell Carcinoma
Neck
Epithelial Cells
Head
Inflammation
Phenotype
Survival
Growth

Keywords

  • Calprotectin
  • Carcinogenesis
  • Cell cycle
  • Differentiation
  • S100A8/A9

Cite this

Involvement of calprotectin (S100A8/A9) in molecular pathways associated with HNSCC. / Khammanivong, Ali; Sorenson, Brent S.; Ross, Karen F; Dickerson, Erin B; Hasina, Rifat; Lingen, Mark W.; Herzberg, Mark C.

In: Oncotarget, Vol. 7, No. 12, 22.03.2016, p. 14029-14047.

Research output: Contribution to journalArticle

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