ABSTRACT
Epigenetics concerns gene regulatory mechanisms beyond DNA sequence，such as DNA methylation，histone modification，chromatin remodeling，and non-coding RNA. Epigenetic mechanisms play a key role in development，cell fate decision and tumorigenesis. Chromatin modifications and its high order structure across our genome are major forms of epigenetic information，and its establishment and maintenance are closely related to cell metabolism. Metabolic changes in cancer cells include aerobic glycolysis，increased glucose uptake，abnormally active glutamine metabolism，and the use of non-conventional energy supply. These changes meet the vigorous energy and matter needs for the development and spread of cancer，and help tumor cells adapt to hypoxia microenvironment for their survival，proliferation，invasion and migration. There is a complex relationship between epigenetic modifications and cell metabolism in tumor. On the one hand，metabolites in tumor cells may act as cofactors，modification donors or antagonists of epigenetic enzymes，thus modulating the epigenetic landscape. On the other hand，epigenetic modifications can directly regulate the expression of metabolic enzymes，transporters，signaling pathway and transcription factors to affect cell metabolism. This article reviews the crosstalk between epigenetics and cancer metabolism，to explore their potential future applications in the treatment of tumors.
Subject(s)
Humans , Carcinogenesis , DNA Methylation , Epigenesis, Genetic , Gene Expression Regulation , Neoplasms/genetics , Tumor MicroenvironmentABSTRACT
El paisaje epigenético es una metáfora gráfica propuesta por Conrad H. Waddington para explicar el desarrollo de los organismos mediante la imagen de un paisaje compuesto por una superficie ondulante con cimas y valles, que representan las vías por las cuales se desplazan las células del organismo en su proceso de diferenciación. C.H. Waddington, considerado como el padre de la epigenética, es notable por sus aportes teóricos, que incluyen las nociones de asimilación genética, la canalización del desarrollo y el epigenotipo. Estas ideas surgieron a partir de estudios experimentales en biología del desarrollo, los cuales resultaron en el descubrimiento del "organizador" en embriones de aves y, posteriormente, de fenocopias inducidas por factores ambientales en Drosophila. En el presente artículo se presenta una interpretación del paisaje epigenético y conceptos relacionados, que ponen en evidencia el poder heurístico de este modelo y su importancia para la biología contemporánea. Este trabajo es un homenaje a la vida de C. H. Waddington, cuya obra continúa siendo de gran actualidad.
The epigenetic landscape is a graphic metaphor proposed by Conrad H. Waddington to explain the development of organisms and their parts. It is depicted as a wavy surface with summits and descending valleys, representing the paths followed by cells along their differentiation process, as part of organismal development. Conrad H. Waddington, regarded as the father of epigenetics, stands out for his theoretical contributions, that include the notions of genetic assimilation, canalization of development and epigenotype. These ideas were inspired by experimental works in developmental biology, that lead to the discovery of the organizer in bird embryos, as well as environmentallyinduced phenocopies in Drosophila. In the current essay, I present an interpretation of the epigenetic landscape and related concepts that highlight the heuristic power of this model and its importance for contemporary biology. This work is a tribute to the life of C. H. Waddington, whose work is still of great significance.