RGD Reference Report - Analysis of Epithelial-Mesenchymal Transition Metabolism Identifies Possible Cancer Biomarkers Useful in Diverse Genetic Backgrounds. - Rat Genome Database

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Analysis of Epithelial-Mesenchymal Transition Metabolism Identifies Possible Cancer Biomarkers Useful in Diverse Genetic Backgrounds.

Authors: Matadamas-Guzman, Meztli  Zazueta, Cecilia  Rojas, Emilio  Resendis-Antonio, Osbaldo 
Citation: Matadamas-Guzman M, etal., Front Oncol. 2020 Jul 30;10:1309. doi: 10.3389/fonc.2020.01309. eCollection 2020.
RGD ID: 152995450
Pubmed: PMID:32850411   (View Abstract at PubMed)
PMCID: PMC7406688   (View Article at PubMed Central)
DOI: DOI:10.3389/fonc.2020.01309   (Journal Full-text)

Epithelial-to-mesenchymal transition (EMT) relates to many molecular and cellular alterations that occur when epithelial cells undergo a switch in differentiation generating mesenchymal-like cells with newly acquired migratory and invasive properties. In cancer cells, EMT leads to drug resistance and metastasis. Moreover, differences in genetic backgrounds, even between patients with the same type of cancer, also determine resistance to some treatments. Metabolic rewiring is essential to induce EMT, hence it is important to identify key metabolic elements for this process, which can be later used to treat cancer cells with different genetic backgrounds. Here we used a mathematical modeling approach to determine which are the metabolic reactions altered after induction of EMT, based on metabolomic and transcriptional data of three non-small cell lung cancer (NSCLC) cell lines. The model suggested that the most affected pathways were the Krebs cycle, amino acid metabolism, and glutathione metabolism. However, glutathione metabolism had many alterations either on the metabolic reactions or at the transcriptional level in the three cell lines. We identified Glutamate-cysteine ligase (GCL), a key enzyme of glutathione synthesis, as an important common feature that is dysregulated after EMT. Analyzing survival data of men with lung cancer, we observed that patients with mutations in GCL catalytic subunit (GCLC) or Glutathione peroxidase 1 (GPX1) genes survived less time than people without mutations on these genes. Besides, patients with low expression of ANPEP, GPX3 and GLS genes also survived less time than those with high expression. Hence, we propose that glutathione metabolism and glutathione itself could be good targets to delay or potentially prevent EMT induction in NSCLC cell lines.

RGD Manual Disease Annotations    Click to see Annotation Detail View
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
lung cancer exacerbatesIAGP 152995450DNA:mutations:multiple (human)RGD 
lung cancer exacerbatesISOGPX1 (Homo sapiens)152995450; 152995450DNA:mutations:multiple (human)RGD 

Objects Annotated

Genes (Rattus norvegicus)
Gpx1  (glutathione peroxidase 1)

Genes (Mus musculus)
Gpx1  (glutathione peroxidase 1)

Genes (Homo sapiens)
GPX1  (glutathione peroxidase 1)


Additional Information