ArticleOral oncology2019
Intracellular calprotectin (S100A8/A9) controls epithelial differentiation and caspase-mediated cleavage of EGFR in head and neck squamous cell carcinoma.
Article in Oral oncology, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.
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Who cites it
14 citing papers in PubMed, 24 citations in OpenAlex.
- Elevated serum calprotectin levels in major depressive disorder: no evidence of association with S100A9 rs3014866 polymorphism.BMC psychiatry · 2026Article
- Calprotectin Levels in HIV-Infected Patients: Correlations With Disease Progression and Intestinal Inflammation.AIDS research and treatment · 2026Article
- Survival prediction in patients with head and neck squamous cell carcinoma and novel mechanistic insights of S100A8/A9.Discover oncology · 2024Article
- Gingerol acts as a potent radiosensitizer in head and neck squamous cell carcinoma.Discover oncology · 2024Article
- Role of innate host defense proteins in oral cancerogenesis.Periodontology 2000 · 2024Review
- S100A8/A9 promotes endometrial fibrosis via regulating RAGE/JAK2/STAT3 signaling pathway.Communications biology · 2024Article
- S100 proteins in head and neck squamous cell carcinoma (Review).Oncology letters · 2023Review
- Expression of S100A9 in adamantinomatous craniopharyngioma and its association with wet keratin formation.Experimental and therapeutic medicine · 2023Article
- MiR-455-5p suppresses PDZK1IP1 to promote the motility of oral squamous cell carcinoma and accelerate clinical cancer invasion by regulating partial epithelial-to-mesenchymal transition.Journal of experimental & clinical cancer research : CR · 2023Article
- Intracellular calprotectin (S100A8/A9) facilitates DNA damage responses and promotes apoptosis in head and neck squamous cell carcinoma.Oral oncology · 2023Article
- The role of interaction between autophagy and apoptosis in tumorigenesis (Review).Oncology reports · 2022Review
- Regulation of zinc-dependent enzymes by metal carrier proteins.Biometals : an international journal on the role of metal ions in biology, biochemistry, and medicine · 2022Review
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Authors and funding
9 authors at 3 institutions in 1 country.
Funding
Abstract
objectivesCalprotectin (S100A8/A9) appears to function as a tumor suppressor in head and neck squamous cell carcinoma (HNSCC) and expression in the carcinoma cells and patient survival rates are directly related. We seek to characterize the suppressive role of calprotectin in HNSCC.
aims(1) Investigate changes in S100A8/A9 expression as oral carcinogenesis progresses and (2) determine whether intracellular calprotectin can regulate epidermal growth factor receptor (EGFR), a negative prognostic factor, in HNSCC. MATERIALS AND
methodsUsing immunohistochemistry (IHC), S100A8/A9 was analyzed in HNSCC specimens (N = 46), including well-differentiated (WD, N = 19), moderately-differentiated (MD, N = 14), poorly-differentiated (PD, N = 5) and non-keratinizing/basaloid (NK/BAS, N = 8), and premalignant epithelial dysplasias (PED, N = 16). Similarly, EGFR was analyzed in HNSCCs (N = 21). To determine whether calprotectin and EGFR expression are mechanistically linked, TR146 HNSCC cells that are S100A8/A9-expressing or silenced (shRNA) were compared for EGFR levels and caspase-3/7 activity using western blotting and immunofluorescence microscopy.
resultsIn normal oral mucosal epithelium, S100A8/A9 stained strongly in the cytoplasm and nucleus of suprabasal cells; basal cells were consistently S100A8/A9 negative. In PED and HNSCC, S100A8/A9 expression was lower than in adjacent normal epithelial tissues (NAT) and declined progressively in WD, MD, PD and NK/BAS HNSCCs. S100A8/A9 and EGFR levels appeared inversely related, which was simulated in vitro when S100A8/A9 was silenced in TR146 cells. Silencing S100A8/A9 significantly reduced caspase-3/7 activity, whereas EGFR levels increased.
conclusionsIn HNSCC, S100A8/A9 is directly associated with cellular differentiation and appears to promote caspase-3/7-mediated cleavage of EGFR, which could explain why patients with S100A8/A9-high tumors survive longer.
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