Ets2 knockdown inhibits tumorigenesis in esophageal squamous cell carcinoma in vivo and in vitro

Oncotarget. 2016 Sep 20;7(38):61458-61468. doi: 10.18632/oncotarget.11369.

Abstract

Increased expression of Ets2 is reported upregulated in esophageal squamous cell carcinoma tissue. However, the function of Ets2 in carcinogenesis of ESCC is poorly understood. Here, the rise of Ets2 was confirmed in ESCC cells and Ets2 depletion by RNA interference promotes cell apoptosis, inhibits cell proliferation, attenuates cell invasion and induces cell cycle G0/G1 arrest in vitro. Moreover, in vivo, Xenograft mouse model studies showed Ets2 knockdown inhibits tumor formation and metastasis significantly. Furthermore, Ets2 depletion inactivates the mTOR/p70S6K signaling pathway both in vitro and in vivo. Taken together, these findings strongly suggest that a critical role of Ets2 in human ESCC pathogenesis via the inactivation of the mTOR/p70S6K signaling pathway.

Keywords: Ets2; apoptosis; esophageal squamous cell carcinoma; mTOR/p70S6K signaling pathway; proliferation.

MeSH terms

  • Animals
  • Apoptosis
  • Carcinogenesis / pathology*
  • Carcinoma, Squamous Cell / pathology*
  • Cell Line, Tumor
  • Cell Proliferation
  • Cell Transformation, Neoplastic
  • Esophageal Neoplasms / pathology*
  • Esophageal Squamous Cell Carcinoma
  • G1 Phase Cell Cycle Checkpoints
  • Gene Knockdown Techniques
  • Humans
  • Male
  • Mice
  • Mice, Inbred BALB C
  • Mice, Nude
  • Proto-Oncogene Protein c-ets-2 / genetics
  • Proto-Oncogene Protein c-ets-2 / metabolism*
  • RNA Interference
  • RNA, Small Interfering / metabolism
  • Ribosomal Protein S6 Kinases, 70-kDa / metabolism*
  • Signal Transduction*
  • Specific Pathogen-Free Organisms
  • TOR Serine-Threonine Kinases / metabolism*
  • Up-Regulation
  • Xenograft Model Antitumor Assays

Substances

  • ETS2 protein, human
  • Proto-Oncogene Protein c-ets-2
  • RNA, Small Interfering
  • MTOR protein, human
  • Ribosomal Protein S6 Kinases, 70-kDa
  • TOR Serine-Threonine Kinases