ArticleBMC cancer2018
Metabolic control of PPAR activity by aldehyde dehydrogenase regulates invasive cell behavior and predicts survival in hepatocellular and renal clear cell carcinoma.
Article in BMC cancer, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.
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Who cites it
17 citing papers in PubMed, 32 citations in OpenAlex.
- In Vitro Cytotoxic Activity ofMolecules (Basel, Switzerland) · 2026Article
- Identification of ALDH7A1 as a DNA-methylation-driven gene in lung squamous cell carcinoma.Annals of medicine · 2025Article
- Tanshinone IIA inhibits heat-induced growth of p53-mutant Huh-7 hepatocellular carcinoma by modulating osmotic homeostasis and glycolysis through targeting ALDH7A1.Cell death discovery · 2025Article
- Association of TP53 with Defective Long Chain 3-Hydroxy acyl-CoA Dehydrogenase Induced Non-Cirrhotic Hepatocellular Carcinoma.Cancers · 2025Article
- Effects of surfactin stress on gene expression and pathological changes in Spodoptera litura.Scientific reports · 2024Article
- Review
- Knockdown of PGBD5 inhibits the malignant progression of glioma through upregulation of the PPAR pathway.International journal of oncology · 2024Article
- Construction of the metabolic reprogramming-associated gene signature for clear cell renal cell carcinoma prognosis prediction.BMC urology · 2023Article
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- Review
- The impact ofAging · 2022Article
- Hybrid Metabolic Activity-Related Prognostic Model and Its Effect on Tumor in Renal Cell Carcinoma.Journal of healthcare engineering · 2022Article
- Role of Metabolic Reprogramming of Long non-coding RNA in Clear Cell Renal Cell Carcinoma.Journal of Cancer · 2022Review
- Screening of possible biomarkers and therapeutic targets in kidney renal clear cell carcinoma: Evidence from bioinformatic analysis.Frontiers in oncology · 2022Article
- Bayesian penalized cumulative logit model for high-dimensional data with an ordinal response.Statistics in medicine · 2021Article
- Article
- Genome-Wide Screen for Context-Dependent Tumor Suppressors Identified Using in Vivo Models for Neoplasia inG3 (Bethesda, Md.) · 2020Article
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Authors and funding
8 authors at 2 institutions in 1 country.
Funding
Abstract
backgroundChanges in cellular metabolism are now recognized as potential drivers of cancer development, rather than as secondary consequences of disease. Here, we explore the mechanism by which metabolic changes dependent on aldehyde dehydrogenase impact cancer development.
methodsALDH7A1 was identified as a potential cancer gene using a Drosophila in vivo metastasis model. The role of the human ortholog was examined using RNA interference in cell-based assays of cell migration and invasion. 1H-NMR metabolite profiling was used to identify metabolic changes in ALDH7A1-depleted cells. Publically available cancer gene expression data was interrogated to identify a gene-expression signature associated with depletion of ALDH7A1. Computational pathway and gene set enrichment analysis was used to identify signaling pathways and cellular processes that were correlated with reduced ALDH7A1 expression in cancer. A variety of statistical tests used to evaluate these analyses are described in detail in the methods section. Immunohistochemistry was used to assess ALDH7A1 expression in tissue samples from cancer patients.
resultsDepletion of ALDH7A1 increased cellular migration and invasiveness in vitro. Depletion of ALDH7A1 led to reduced levels of metabolites identified as ligands for Peroxisome proliferator-activated receptor (PPARα). Analysis of publically available cancer gene expression data revealed that ALDH7A1 mRNA levels were reduced in many human cancers, and that this correlated with poor survival in kidney and liver cancer patients. Using pathway and gene set enrichment analysis, we establish a correlation between low ALDH7A1 levels, reduced PPAR signaling and reduced patient survival. Metabolic profiling showed that endogenous PPARα ligands were reduced in ALDH7A1-depleted cells. ALDH7A1-depletion led to reduced PPAR transcriptional activity. Treatment with a PPARα agonist restored normal cellular behavior. Low ALDH7A1 protein levels correlated with poor clinical outcome in hepatocellular and renal clear cell carcinoma patients.
conclusionsWe provide evidence that low ALDH7A1 expression is a useful prognostic marker of poor clinical outcome for hepatocellular and renal clear cell carcinomas and hypothesize that patients with low ALDH7A1 might benefit from therapeutic approaches addressing PPARα activity.
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