Prognostic significance and function of the vacuolar H+-ATPase subunit V1E1 in esophageal squamous cell carcinoma

Sung Wook Son, Seok Hyung Kim, Eun Yi Moon, Dong-Hun Kim, Suhkneung Pyo, Sung Hee Um

Research output: Contribution to journalArticle

2 Citations (Scopus)

Abstract

Vacuolar H+-ATPase (V-ATPase), a hetero-multimeric ATP-driven proton pump has recently emerged as a critical regulator of mTOR-induced amino acid sensing for cell growth. Although dysregulated activity of cell growth regulators is often associated with cancer, the prognostic significance and metabolic roles of V-ATPase in esophageal cancer progression remain unclear. Here, we show that high levels of V-ATPase subunit V1E1 (V-ATPase V1E1) were significantly associated with shortened disease-free survival in patients with esophageal squamous cell carcinoma (ESCC). Multivariate analysis identified the V-ATPase V1E1 as an independent adverse prognostic factor (hazard ratio;1.748, P = 0.018). In addition, depletion of V-ATPase V1E1 resulted in reduced cell motility, decreased glucose uptake, diminished levels of lactate, and decreased ATP production, as well as inhibition of glycolytic enzyme expression in TE8 esophageal cancer cells. Consistent with these results, the Cancer Genome Atlas (TCGA) data and Gene Set Enrichment Analysis (GSEA) showed a high frequency of copy number alterations of the V-ATPase V1E1 gene, and identified a correlation between levels of V-ATPase V1E1 mRNA and Pyruvate Kinase M2 (PKM2) in ESCC. High expression levels of both V-ATPase V1E1 and phosphorylated PKM2 (p-PKM2), a key player in cancer metabolism, were associated with poorer prognosis in ESCC. Collectively, our findings suggest that expression of the V-ATPase V1E1 has prognostic significance in ESCC, and is closely linked to migration, invasion, and aerobic glycolysis in esophageal cancer cells.

Original languageEnglish
Pages (from-to)49334-49348
Number of pages15
JournalOncotarget
Volume7
Issue number31
DOIs
Publication statusPublished - 2016

Fingerprint

Vacuolar Proton-Translocating ATPases
Esophageal Neoplasms
Pyruvate Kinase
Adenosine Triphosphate
Esophageal Squamous Cell Carcinoma
Proton Pumps
Neoplasms
Atlases
Glycolysis
Growth
Genes
Disease-Free Survival
Cell Movement
Lactic Acid
Multivariate Analysis
Genome
Amino Acids
Glucose
Messenger RNA

Keywords

  • Aerobic glycolysis
  • Cell motility
  • Esophageal squamous cell carcinoma (ESCC)
  • Prognosis
  • V-ATPase subunit V1E1

ASJC Scopus subject areas

  • Oncology

Cite this

Prognostic significance and function of the vacuolar H+-ATPase subunit V1E1 in esophageal squamous cell carcinoma. / Son, Sung Wook; Kim, Seok Hyung; Moon, Eun Yi; Kim, Dong-Hun; Pyo, Suhkneung; Um, Sung Hee.

In: Oncotarget, Vol. 7, No. 31, 2016, p. 49334-49348.

Research output: Contribution to journalArticle

Son, Sung Wook ; Kim, Seok Hyung ; Moon, Eun Yi ; Kim, Dong-Hun ; Pyo, Suhkneung ; Um, Sung Hee. / Prognostic significance and function of the vacuolar H+-ATPase subunit V1E1 in esophageal squamous cell carcinoma. In: Oncotarget. 2016 ; Vol. 7, No. 31. pp. 49334-49348.
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