Integrin α6 promotes esophageal cancer metastasis and is targeted by miR-92b

Oncotarget. 2017 Jan 24;8(4):6681-6690. doi: 10.18632/oncotarget.14259.

Abstract

Tumor invasion and metastasis is responsible for the poor prognosis of esophageal squamous cell carcinoma (ESCC); therefore, exploring the mechanisms by which malignant cells disseminate, spread and flourish in secondary sites, as well as translating the bench results to clinical practice are in urgent need. Previous reports showed that integrin α6 increases in ESCC specimens and its dysregulated spatial localization correlates positively with the unfavorable outcome of ESCC patients. Here, we clarify that integrin α6 promotes invasion and metastasis of ESCC cells In vitro and in vivo. Mechanistically, decreased integrin α6 attenuates motility of malignant cells partially through deactivating Akt pathway, which is essential for ESCC cells motility. Moreover, integrin α6 serves as a genuine target of miR-92b in suppressing ESCC motility. Our results for the first time describe that miR-92b/integrin α6/Akt axis controls the motility of ESCC, thereby providing a promising diagnosis or therapeutic option.

Keywords: esophageal cancer; integrin α6; metastasis; microRNA-92b.

MeSH terms

  • Animals
  • Carcinoma, Squamous Cell / genetics
  • Carcinoma, Squamous Cell / metabolism*
  • Carcinoma, Squamous Cell / secondary
  • Cell Line, Tumor
  • Cell Movement*
  • Esophageal Neoplasms / genetics
  • Esophageal Neoplasms / metabolism*
  • Esophageal Neoplasms / pathology
  • Esophageal Squamous Cell Carcinoma
  • Female
  • Gene Expression Regulation, Neoplastic
  • Humans
  • Integrin alpha6 / genetics
  • Integrin alpha6 / metabolism*
  • Lung Neoplasms / genetics
  • Lung Neoplasms / metabolism*
  • Lung Neoplasms / secondary
  • Lymphatic Metastasis
  • Male
  • Mice
  • MicroRNAs / genetics
  • MicroRNAs / metabolism*
  • Middle Aged
  • Proto-Oncogene Proteins c-akt / metabolism
  • Signal Transduction
  • Time Factors

Substances

  • ITGA6 protein, human
  • Integrin alpha6
  • MIRN92 microRNA, human
  • MicroRNAs
  • Proto-Oncogene Proteins c-akt