Epigenetic mechanisms in senescence, immortalisation and cancer.
Cancer is controlled not only by genetic events but also by epigenetic events. The active acquisition of epigenetic changes is a poorly understood but very important process in mammalian development, differentiation, and disease. It is well established that epigenetic events are controlled by a specific subgroup of proteins, such as DNA methyltransferases, histone acetylases histone lysine methyltransferases or histone deacetylases, that influence methylation or acetylation patterns to modulate gene expression. We and others have identified S-adenosylhomocysteine hydrolase in a high-throughput genetic screen focused on discovering novel genes whose inhibition induces immortalisation of primary cells. Herein, we address the importance of genes involved in epigenetic mechanisms during senescence and how their effects might determine senescence bypass and immortalisation. The ways in which genes that regulate epigenetic mechanisms might modulate senescence/immortalisation and how these pathways could influence cancer development are explored. Overall, epigenetic modifications seem to play a major role in cancer, influencing tumour outcome by interfering with key senescence pathways.
Carnero
Amancio
A
Instituto de Biomedicina de Sevilla, Hospital Universitario Virgen del Rocio, Av. Manuel Siurot s/n, Seville, Spain. acarnero@ibis-sevilla.es
Lleonart
Matilde E
ME
D000375:Aging / Q000235:genetics* / Q000502:physiology*; D044127:Epigenesis, Genetic; D006801:Humans; D009369:Neoplasms / Q000235:genetics* / Q000378:metabolism*