Mitochondrial Metabolism as a Potential Novel Therapeutic Target for Lung Adenocarcinoma.

IF 1.6 4区 医学 Q4 ONCOLOGY
Makoto Fujiwara, Takahiro Mimae, Kei Kushitani, Norifumi Tsubokawa, Yoshihiro Miyata, Yukio Takeshima, Morihito Okada
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引用次数: 0

Abstract

Background/aim: Oxidative phosphorylation (OXPHOS) is implicated in cancer progression and metastasis. However, its role in lung adenocarcinoma (LUAD) is unknown. We assessed OXPHOS in LUAD cases and cell lines and investigated the effect of OXPHOS inhibition on LUAD cells.

Materials and methods: The cases with high expression of OXPHOS-related genes and peroxisome proliferator-activated receptor gamma (PPAR-γ) were extracted using RNA-seq data from The Cancer Genome Atlas (TCGA) LUAD dataset and the clinicopathological features and survival were assessed. Resected LUAD specimens were stained for PPAR-γ. Real-time qPCR and western blot were used to examine the expression of OXPHOS- and glycolysis-related genes and proteins in four LUAD cell lines. Cell proliferation was evaluated in LUAD cells treated with OXPHOS inhibitors.

Results: The TCGA database analysis revealed that cases with high OXPHOS or PPAR-γ expression had a worse prognosis (p=0.07 and p=0.01, respectively). High OXPHOS cases were associated with lymph node metastasis (p<0.01). PPAR-γ was expressed only in the peripheral area of the papillary component of LUAD. We identified A549, HTB181 and H322 as OXPHOS-high type cells and H596 as OXPHOS-low type cells. Oligomycin treatment inhibited cell proliferation in the OXHOS-high cells (0.72-, 0.69-, and 0.77- fold change in oligomycin vs. DMSO, for A549, HTB181, and H322 cells, respectively, p<0.01) but not in the OXPHOS-low cells.

Conclusion: High expression of OXPHOS-related genes and PPAR-γ is a poor prognostic factor in LUAD. The levels of OXPHOS vary among cases and within different areas of the tumor. Targeting OXPHOS metabolism may represent a novel therapeutic approach for treating LUAD.

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来源期刊
Anticancer research
Anticancer research 医学-肿瘤学
CiteScore
3.70
自引率
10.00%
发文量
566
审稿时长
2 months
期刊介绍: ANTICANCER RESEARCH is an independent international peer-reviewed journal devoted to the rapid publication of high quality original articles and reviews on all aspects of experimental and clinical oncology. Prompt evaluation of all submitted articles in confidence and rapid publication within 1-2 months of acceptance are guaranteed. ANTICANCER RESEARCH was established in 1981 and is published monthly (bimonthly until the end of 2008). Each annual volume contains twelve issues and index. Each issue may be divided into three parts (A: Reviews, B: Experimental studies, and C: Clinical and Epidemiological studies). Special issues, presenting the proceedings of meetings or groups of papers on topics of significant progress, will also be included in each volume. There is no limitation to the number of pages per issue.
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