Do high incidences of common neoplasms depend on evolutionary abandoned regulatory loops revived in tumor cells by mutations?
Neoplasms seem much more common than one might expect, considering complexity of the required cell malfunctions. It seems very unlikely to get them all set in the single cell by pure chance. Here presented idea is neoplasms exploit evolutionary abandoned regulatory mechanisms still contained in our genome. During evolution numerous changes have occurred in cell biology of multicellular organisms. Regulatory mechanisms developed, modified its affinity, sensitivity, and effects on different cells. Some eventually disappeared. Others got another chance to get involved in something different. Most of these changes are forever lost, but, inevitably, our genome contains codes for proteins that still can serve abandoned regulatory mechanisms that are not active in normal cells. Transformation from normal to malignant cells depends on accumulated alterations that remain compatible with cell survival and this can happen if alterations critical for cell survival activate old regulatory loops, obsolete in normal cells. Otherwise, mutated cells would die before becoming malignant. Based on this concept of ever-changing cellular function within survival limited borders, living cells can be considered confined in a well-defined time-space continuum that incorporate occurrence and disappearance of macromolecules, metabolites, mediators and physical influences. Numerous scenarios involving the same set of regulatory proteins emerged during evolution. All survival compatible scenarios were passed to next generations and many times retested. Evolutionary conservation of important proteins saved also all existing possibilities of interactions between them, so parts of abandoned scenarios can be activated in malignant cells. This box of forgotten tools in our genome might be the prerequisite of high incidences reported for common neoplasms.
Kurbel
Sven
S
Osijek Medical Faculty, Department of Physiology, J Huttlera 4, 31000 Osijek, Croatia. sven@jware.hr
D002471:Cell Transformation, Neoplastic; D019143:Evolution, Molecular; D015972:Gene Expression Regulation, Neoplastic; D015994:Incidence; D008954:Models, Biological; D009154:Mutation; D009369:Neoplasms / Q000453:epidemiology* / Q000235:genetics* / Q000473:pathology