TRIM44 promotes human esophageal cancer progression via the AKT/mTOR pathway

Cancer Sci. 2018 Oct;109(10):3080-3092. doi: 10.1111/cas.13762. Epub 2018 Aug 28.

Abstract

Aberrant expression of TRIM-containing protein 44 (TRIM44) acts as a promoter in multiple cancers. Here, we investigated the biological functions and clinical significance of TRIM44 in human esophageal cancer (HEC). TRIM44 expression was significantly higher in HEC tissues than corresponding normal tissues at both the mRNA (2.42 ± 0.52 vs 0.99 ± 0.25) and protein (1.01 ± 0.27 vs 0.30 ± 0.13) levels. Patients with high TRIM44 expression showed poor differentiation (P = 1.39 × 10-5 ), advanced TNM stage (P = 3.87 × 10-4 ) and, most importantly, significantly poorer prognosis (P = 2.80 × 10-5 ). TRIM44 played a crucial role in epithelial mesenchymal transition (EMT). A significant correlation was observed between TRIM44 and Ki67 expression. We demonstrated that TRIM44 markedly enhanced HEC cell proliferation, migration, and invasion. Additionally, TRIM44 was involved in the AKT/mTOR signaling pathway and its downstream targets, such as STAT3 phosphorylation. Thus, elevated TRIM44 expression promotes HEC development by EMT via the AKT/mTOR pathway, and TRIM44 may be a novel prognostic indicator for HEC patients after curative resection.

Keywords: EMT; HEC; TRIM44; prognosis; survival.

MeSH terms

  • Aged
  • Carrier Proteins / genetics
  • Carrier Proteins / metabolism*
  • Cell Line, Tumor
  • Disease Progression
  • Epithelial-Mesenchymal Transition*
  • Esophageal Neoplasms / mortality
  • Esophageal Neoplasms / pathology*
  • Esophageal Neoplasms / surgery
  • Esophagectomy
  • Esophagus / pathology
  • Female
  • Gene Knockdown Techniques
  • Humans
  • Intracellular Signaling Peptides and Proteins
  • Kaplan-Meier Estimate
  • Ki-67 Antigen / metabolism
  • Male
  • Middle Aged
  • Neoplasm Staging
  • Phosphorylation
  • Prognosis
  • Proto-Oncogene Proteins c-akt / metabolism*
  • STAT3 Transcription Factor / metabolism
  • Signal Transduction
  • TOR Serine-Threonine Kinases / metabolism*
  • Tripartite Motif Proteins

Substances

  • Carrier Proteins
  • Intracellular Signaling Peptides and Proteins
  • Ki-67 Antigen
  • STAT3 Transcription Factor
  • STAT3 protein, human
  • TRIM44 protein, human
  • Tripartite Motif Proteins
  • MTOR protein, human
  • Proto-Oncogene Proteins c-akt
  • TOR Serine-Threonine Kinases