An international team with seven institutions from Spain and the US participating in the University of Valencia has discovered for the first time that the biological activity of the c-MYC gene is necessary so that cell reprogramming occurs, that is, the process by which a specialised cell –for example, a neuron– is transformed into a different cell type. According to the results published in Stem Cell Reports magazine, internal cellular activity favoured by the genes of the MYC family may be the cause of any cellular transformation
The study carried out by Javier Prieto (first author of the work), Xavier Ponsoda, Salva Martí, Marian León, Carlos López and Josema Torres (director of the work), of the Department of Cell Biology, Functional Biology and Physical Anthropology of The University of Valencia, completely disassembles the previous paradigm around how the c-MYC gene affects cellular reprogramming. The article published in the journal of the International Society for Stem Cell Research (ISCCR) describes a remodelling of mitochondrial dynamics and metabolism by the c-MYC gene during the first phase of this process.
“Our results show for the first time that the biological activity of the MYC gene family is necessary to transform a somatic cell into a pluripotent cell that, when becoming different, can originate any cell of the adult organism. Due to the parallelisms between the described reprogramming process and the cellular transformation carried out by oncogenes, our results suggest that endogenous MYC genes may be behind the action of these oncogenes to transform a normal cell into a cancer one. In this way, the MYC proteins are identified as possible therapeutic targets in tumours where they are not directly responsible as oncogenes”, said Josema Torres, a researcher associated with INCLIVA.
Thus, prior to this study, it was believed that during cell reprogramming, oxidative phosphorylation was cancelled. This is a metabolic process that uses the energy released by the oxidation of nutrients to produce ATP, a molecule used to generate energy to the chemical reactions that occur within the organism. At the same time, it was thought that this process was cancelled during cell reprogramming, and it was also thought that glycolysis occurred (a succession of chemical reactions through which the cell obtained energy from the glucose).
The new results demonstrate the importance of metabolic processes for cell reprogramming, where the protein that governs this process is c-MYC. And in addition, we prove that during this transformation a process called bivalent or hybrid metabolism takes place, in which both oxidative phosphorylation and glycolysis occur.
MYC genes, a group of which c-MYC is a part, belong to the family of protooncogens and are those that promote cell division. These genes are found in the nucleus of the cells and encode proteins. Therefore, they regulate the activity of other genes. In the transformation, for example, of a somatic cell (any cell of the bones, tissues, organs, blood, or skin of the human body), it is very probable that metabolic changes are needed as a result of its gene c-MYC so that this process takes place.
The research has been funded by the European Regional Development Fund of the European Union (ERDF), the Ministry of Economy and Business and the Ramón Areces Foundation.
Article:
Prieto et al., «MYC Induces a Hybrid Energetics Program Early in Cell Reprogramming», Stem Cell Reports (2018) https://doi.org/10.1016/j.stemcr.2018.10.018
