Balamurli, G., Liew, A. Q. X., Tee, W. W., & Pervaiz, S. (2024). Interplay between epigenetics, senescence and cellular redox metabolism in cancer and its therapeutic implications. Redox Biology, 78, 103441. https://doi.org/10.1016/j.redox.2024.103441
Abstract:
There is accumulating evidence indicating a close crosstalk between key molecular events regulating cell growth and proliferation, which could profoundly impact carcinogenesis and its progression. Here we focus on reviewing observations highlighting the interplay between epigenetic modifications, irreversible cell cycle arrest or senescence, and cellular redox metabolism. Epigenetic alterations, such as DNA methylation and histone modifications, dynamically influence tumour transcriptome, thereby impacting tumour phenotype, survival, growth and spread. Interestingly, the acquisition of senescent phenotype can be triggered by epigenetic changes, acting as a double-edged sword via its ability to suppress tumorigenesis or by facilitating an inflammatory milieu conducive for cancer progression. Concurrently, an aberrant redox metabolism, which is a function of the balance between reactive oxygen species (ROS) generation and intracellular anti-oxidant defences, influences signalling cascades and genomic stability in cancer cells by serving as a critical link between epigenetics and senescence. Recognizing this intricate interconnection offers a nuanced perspective for therapeutic intervention by simultaneously targeting specific epigenetic modifications, modulating senescence dynamics, and restoring redox homeostasis.
License type:
Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0)
Funding Info:
This research / project is supported by the National Research Foundation - National Research Foundation Fellowship
Grant Reference no. : NRF-NRFF2016-06
This research / project is supported by the National Medical Research Council - Open Fund - Young Individual Research Grant
Grant Reference no. : NMRC-OFIRG21 nov-0027