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NADH dehydrogenase complex I is overexpressed in incipient metastatic murine colon cancer cells. | LitMetric

AI Article Synopsis

  • Colon cancer is a common cancer, and while primary tumors are treatable, metastatic cases often lead to severe outcomes.
  • The study investigated how primary colon cancer cells transition to metastatic forms, focusing on protein expression changes and utilizing a specially developed mouse cancer cell line.
  • Findings showed that metastatic cells overexpress NADH dehydrogenase complex I but accumulate more NADH and reactive oxygen species, suggesting a shift in energy metabolism, which could be targeted in future anti-metastatic therapies.

Article Abstract

Colon cancer is one of the most frequently occurring types of cancers in the world. Primary tumours are treated very efficiently, but the metastatic cases are known to have severe outcomes. Therefore, the aim of the present study was to obtain a greater understanding of the transformation of primary colon cancer cells into metastatic phenotypes. Small changes in protein expression provoke the metastatic phenotype transformation. More sensitive methods to detect small variations are required. A murine colon cancer cell line with metastatic characteristics in a very early phase was created in order to investigate the first steps of transformation using a murine liver metastasis model. The protein expression patterns of metastatic and non‑metastatic cells were compared using the stable isotope labelling by amino acids in cell culture method in combination with mass spectrometry. Quantitative proteomics data indicated that nicotinamide adenine dinucleotide hydride (NADH) dehydrogenase complex I was overexpressed in metastatic cells with respect to non‑metastatic cells. Since the NADH dehydrogenase complex catalyses the oxidation of NADH to NAD+, the functionality of the complex was studied by measuring the amount of NADH. The results revealed that metastatic cells accumulate more NADH and reactive oxygen species. In addition, the mitochondrial membrane potential of metastatic cells was lower than that of non‑metastatic cells, indicating that the activity of NADH dehydrogenase and the mitochondrial oxidative chain were decreased in metastatic cells. During the incipient transformation of primary cancer cells, NADH dehydrogenase complex I was overexpressed but then became inactive due to the Warburg effect, which inhibits mitochondrial activity. In the first step of transformation, the high energy demand required in an adverse environment is fulfilled by overexpressing components of the respiratory chain, a fact that should be considered for future anti‑metastatic therapies.

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Source
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6313061PMC
http://dx.doi.org/10.3892/or.2018.6892DOI Listing

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