The calcimedin annexin A3 displays tumor-promoting effect in esophageal squamous cell carcinoma by activating NF-κB signaling

Mamm Genome. 2021 Oct;32(5):381-388. doi: 10.1007/s00335-021-09883-3. Epub 2021 Jun 9.

Abstract

Esophageal squamous cell carcinoma (ESCC) is one of the lethal malignancies commonly found in the eastern world, with overall five-year survival rates less than 25%. The present study aimed to investigate the biological function of annexin A3 (ANXA3) in ESCC cell proliferation. The mRNA and protein levels of ANXA3 in ESCC tissues and cell lines were determined by real-time PCR and Western blot, respectively. Lentiviral transduction was applied to overexpress or reduce ANXA3 expression in ESCC cell lines. The effect of ANXA3 on ESCC cell proliferation was evaluated by cell-counting kit-8 assay in vitro and tumor-bearing animal model in vivo. We found that ANXA3 was substantially upregulated in ESCC tissues compared to adjacent normal tissues as well as ESCC cell lines compared to normal esophageal endothelial cells. Suppression of ANXA3 significantly inhibited ESCC cell proliferation in vitro and tumor growth in vivo. We further revealed that NF-κB was involved in ANXA3-mediated ESCC cell proliferation. Our results suggest that ANXA3 acts as an oncogene in ESCC, and targeting ANXA3 or NF-κB may serve as potential therapeutic strategies for patients with ESCC.

MeSH terms

  • Animals
  • Annexin A3 / physiology*
  • Cell Line, Tumor
  • Esophageal Neoplasms / metabolism*
  • Esophageal Squamous Cell Carcinoma / metabolism*
  • Humans
  • Mice
  • Mice, Inbred BALB C
  • Mice, Nude
  • NF-kappa B / metabolism*
  • Signal Transduction*

Substances

  • ANXA3 protein, human
  • NF-kappa B
  • Annexin A3