Promotion of glioma cell survival by acyl-CoA synthetase 5 under extracellular acidosis conditions

T. Mashima, S. Sato, Yoshikazu Sugimoto, T. Tsuruo, H. Seimiya

Research output: Contribution to journalArticle

37 Citations (Scopus)

Abstract

Extracellular acidosis (low pH) is a tumor microenvironmental stressor that has a critical function in the malignant progression and metastatic dissemination of tumors. To survive under stress conditions, tumor cells must evolve resistance to stress-induced toxicity. Acyl-CoA synthetase 5 (ACSL5) is a member of the ACS family, which converts fatty acid to acyl-CoA. ACSL5 is frequently overexpressed in malignant glioma, whereas its functional significance is still unknown. Using retrovirus-mediated stable gene transfer (gain of function) and small interfering RNA-mediated gene silencing (loss of function), we show here that ACSL5 selectively promotes human glioma cell survival under extracellular acidosis. ACSL5 enhanced cell survival through its ACS catalytic activity. To clarify the genome-wide changes in cell signaling pathways by ACSL5, we performed cDNA microarray analysis and identified an ACSL5-dependent gene expression signature. The analysis revealed that ACSL5 was critical to the expression of tumor-related factors including midkine (MDK), a heparin-binding growth factor frequently overexpressed in cancer. Knockdown of MDK expression significantly attenuated ACSL5-mediated survival under acidic state. These results indicate that ACSL5 is a critical factor for survival of glioma cells under acidic tumor microenvironment, thus providing novel molecular basis for cancer therapy.

Original languageEnglish
Pages (from-to)9-19
Number of pages11
JournalOncogene
Volume28
Issue number1
DOIs
Publication statusPublished - 2009 Jan 8

Fingerprint

Acidosis
Glioma
Cell Survival
Neoplasms
Acyl Coenzyme A
Tumor Microenvironment
Gene Silencing
Retroviridae
Microarray Analysis
Oligonucleotide Array Sequence Analysis
Transcriptome
Small Interfering RNA
Heparin
acyl CoA synthetase 5
Intercellular Signaling Peptides and Proteins
Fatty Acids
Genome
Survival
Genes

Keywords

  • Acyl-CoA synthetase
  • Lipid metabolism
  • Low pH
  • Microenvironment
  • Midkine

ASJC Scopus subject areas

  • Molecular Biology
  • Cancer Research
  • Genetics

Cite this

Promotion of glioma cell survival by acyl-CoA synthetase 5 under extracellular acidosis conditions. / Mashima, T.; Sato, S.; Sugimoto, Yoshikazu; Tsuruo, T.; Seimiya, H.

In: Oncogene, Vol. 28, No. 1, 08.01.2009, p. 9-19.

Research output: Contribution to journalArticle

Mashima, T. ; Sato, S. ; Sugimoto, Yoshikazu ; Tsuruo, T. ; Seimiya, H. / Promotion of glioma cell survival by acyl-CoA synthetase 5 under extracellular acidosis conditions. In: Oncogene. 2009 ; Vol. 28, No. 1. pp. 9-19.
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