Rap1A promotes esophageal squamous cell carcinoma metastasis through the AKT signaling pathway

Oncol Rep. 2019 Nov;42(5):1815-1824. doi: 10.3892/or.2019.7309. Epub 2019 Sep 12.

Abstract

Ras‑associated protein 1A (Rap1A) is a member of the Ras subfamily of small GTP‑binding proteins and is found to promote metastasis in several types of cancer. However, the functional role and molecular mechanism of action in Rap1A in esophageal squamous cell carcinoma (ESCC) is not fully understood. In the present study, Rap1A was found to be upregulated in ESCC tissues and its expression was correlated with cancer stage. Functional studies revealed that Rap1A could promote ESCC metastasis by stimulating cell migration and invasion in vivo and in vitro. Further study indicated that the transcriptional factor SP1 increased Rap1A expression via promoter binding and transcription activation. Furthermore, Rap1A promoted epithelial‑to‑mesenchymal transition, possibly through the AKT signaling pathway. Hence, the findings of the present study indicated that Rap1A may be a potential prognostic marker or therapeutic target for ESCC.

MeSH terms

  • Animals
  • Cell Line, Tumor
  • Epithelial-Mesenchymal Transition
  • Esophageal Neoplasms / genetics
  • Esophageal Neoplasms / metabolism
  • Esophageal Neoplasms / pathology*
  • Esophageal Squamous Cell Carcinoma / genetics
  • Esophageal Squamous Cell Carcinoma / metabolism
  • Esophageal Squamous Cell Carcinoma / pathology*
  • Female
  • Gene Expression Regulation, Neoplastic
  • Humans
  • Mice
  • Neoplasm Staging
  • Neoplasm Transplantation
  • Promoter Regions, Genetic
  • Proto-Oncogene Proteins c-akt / metabolism
  • Signal Transduction
  • Sp1 Transcription Factor / metabolism*
  • Up-Regulation
  • rap1 GTP-Binding Proteins / genetics*
  • rap1 GTP-Binding Proteins / metabolism*

Substances

  • RAP1A protein, human
  • Sp1 Transcription Factor
  • SP1 protein, human
  • Proto-Oncogene Proteins c-akt
  • rap1 GTP-Binding Proteins