Evolutionary Origins of Metabolic Reprogramming in Cancer

Int J Mol Sci. 2022 Oct 11;23(20):12063. doi: 10.3390/ijms232012063.

Abstract

Metabolic changes that facilitate tumor growth are one of the hallmarks of cancer. These changes are not specific to tumors but also take place during the physiological growth of tissues. Indeed, the cellular and tissue mechanisms present in the tumor have their physiological counterpart in the repair of tissue lesions and wound healing. These molecular mechanisms have been acquired during metazoan evolution, first to eliminate the infection of the tissue injury, then to enter an effective regenerative phase. Cancer itself could be considered a phenomenon of antagonistic pleiotropy of the genes involved in effective tissue repair. Cancer and tissue repair are complex traits that share many intermediate phenotypes at the molecular, cellular, and tissue levels, and all of these are integrated within a Systems Biology structure. Complex traits are influenced by a multitude of common genes, each with a weak effect. This polygenic component of complex traits is mainly unknown and so makes up part of the missing heritability. Here, we try to integrate these different perspectives from the point of view of the metabolic changes observed in cancer.

Keywords: cancer; evolution; heritability; inflammation; intermediate phenotypes; regenerative phase; tissue repair.

Publication types

  • Review

MeSH terms

  • Animals
  • Neoplasms* / genetics
  • Phenotype
  • Systems Biology

Grants and funding

This work was supported in JPL’s lab by Grant PID2020-118527RB-I00 funded by MCIN/AEI/10.13039/501100011039; Grant PDC2021-121735-I00 funded by MCIN/AEI/10.13039/501100011039 and by the “European Union Next Generation EU/PRTR.”, the Regional Government of Castile and León (CSI234P18 and CSI144P20). SCLl was the recipient of a Ramón y Cajal research contract from the Spanish Ministry of Economy and Competitiveness and was supported by grant RTI2018-094130-B-100 funded by MCIN/AEI/10.13039/501100011039 and by “ERDF A way of making Europe.” RCC and AJN are funded by fellowships from the Spanish Regional Government of Castile and León. NGS is a recipient of an FPU fellowship (MINECO/FEDER). MJPB is funded by grant PID2020-118527RB-I00 funded by MCIN/AEI/10.13039/501100011039. J.C. is partially supported by grant GRS2139/A/20 (Gerencia Regional de Salud de Castilla y León) and by the Instituto de Salud Carlos III (PI18/00587 and PI21/01207), co-financed by FEDER funds, and by the “Programa de Intensificación” of the ISCIII, grant number INT20/00074. We thank Phil Mason for English language support.