Carcinogenesis and Endocrine Pancreas Deficiency: A Working Frame for Cancer Prevention or Treatment

Abstract

In Cancer, a metabolic rewiring of biochemical pathways supports tumor cell anabolism, while body reserves are depleted by catabolic hormone. Wepreviously analyzed in detail the downstream phosphorylation of enzymes supporting the metabolic rewiring observed in cancer and found thatthe hybrid-anabolic or catabolic status of tumor cellsenzymeswould be explained by alteration of the endocrine pancreas. It is like if beta cells secreting anabolic insulin failed to silence with gamma aminobutyric acid (GABA), neighboring alpha and delta cells, releasing catabolic glucagon and somatostatin respectively. Moreover, the GABA deficiency, would alsofail to turn off insulin release leading to a progressive desensitization of insulin receptors on differentiated cells, selectively sensitive to glucagon. This explains the depletion of tissue reserves for the benefit of mitotic cells with new,non-desensitized insulin receptors,such cellswill then display the hybrid rewired metabolic response. At this initialstage the metabolic advantagegained by these stem cells is reversible,giving new therapeutic possibilities for preventing their transformation into aggressive tumors. We propose that stem cells that repair tissues after an injurymight start the carcinogenic process, if there is an associated pancreaticfailure that rewires their metabolic pathways. This is discussed in relation to Nutrition, Diabetes type 2 and to factors increasing cancer incidence