*Oncogenesis eventuates genetic mutation to epigenetic gene expression mechanisms with molecular signatures either inappropriately proscribed, incorrectly prescribed upon writing as dangerous and deleterious, or erasure; leaving a corrupted chromatin result.
*Tumor cells obtain proliferative autonomy, autophagous –self-maintenance in growth and signaling, neovascularization for nutrient and oxygen supply, and resistance to anti-proliferative and apoptotic stimuli
*In resting cells, the cell cycle is strictly managed by a set of regulatory proteins that control the various cell cycle checkpoints and this will become dysfunction during the early transforming stage of the tumorigenesis via the unregulated dismantling of tumor suppressor genes
*Suppression is the programmed deliberative inhibition of biochemical events while repression is the unintentional inhibition of biochemical events
*When a biochemical event is de-repressed it is brought back to register, regardless of valence
*In effect this dismantling is a repression of tumor suppressor gene transcription and/or translation, post-translational modifications or final agency
*This loss of gene suppressor “activity” can result from deletion, inactivating mutations, epigenetic silencing, incoherent post-translational modification(s) including glycosylation/acylation/prenylation/phosphorylation/aggregation etc.or lipid mediated transport aberrations as with membrane lipid rafts from Sphingomyelinase mediated ceramide synthesis.
*The typical biomedical result is oncogenesis(transformative) and ultimately tumorigenesis (committed), metastasis (mobilized and transactional) and either death or repair to healthy state.
*The progression of the mammalian cell cycle from G1 to mitosis is regulated by cyclins with their cogent catalytic subunits, the referred to as cyclin-dependent kinases (CDKs)
*A family of cyclin–CDK inhibitor proteins (CDIs), which bind and inactivate the CDKs, includes the p16INK4a, p21CIP1, p27KIP1, and associated proteins p15INK4b, p18INK4c, p19INK4d and p57KIP2
*These proteins potentially act as tumor suppressors and their inactivation corresponds with human carcinogenesis.
*Selective removal of CDK inhibitors may ablate senescent cell lineages in a process known as senolysis which may promote healthy cardiac muscle aging in the elderly
* In balance the square of opposition logical conclusion is to distinguish between contrarion vs. contradictory physiological and pharmaco-therapies.
Dr Daniel J. Guerra Authentic Biochemistry Published on 10 February 2021
Refs
EBioMedicine 2016 830-39DOI: (10.1016)
BMC Cancer volume 20, Article number: 882 (2020)
J Cardiol. 2019 Oct;74(4):313-319
Front. Neurosci., 24 July 2019 | https://doi.org/10.3389/fnins.2019.00728