Mammalian tumor-like organs. 2. Mammalian adipose has many tumor features and obesity is a tumor-like process

Abstract

Background In previous publications, the author developed the theory of carcino-evo-devo, which predicts that evolutionarily novel organs should recapitulate some features of tumors in their development. Main text Mammalian adipose is currently recognized as a multi-depot metabolic and endocrine organ consisting of several adipose tissues. Although lipid-storing cells and proteins are ancient, the adipose organ as a whole is evolutionarily novel to mammals. The adipose expansion has remarkable similarities with the growth of solid tumors. These similarities are the following: (1) The capability to unlimited expansion; (2) Reversible plasticity; (3) Induction of angiogenesis; (4) Chronic inflammation; (5) Remodeling and disfunction; (6) Systemic influence on the organism; (7) Hormone production; (8) Production of miRNAs that influence other tissues; (9) Immunosuppression; (10) DNA damage and resistance to apoptosis; (11) Destructive infiltration in other organs and tissues. These similarities include the majority of “hallmarks of cancer”. In addition, lipomas are the most frequent soft tissue tumors, and similar drugs may be used for the treatment of obesity and cancer by preventing infiltration. This raises the possibility that obesity, at least in part, may represent an oncological problem. The existing similarities between adipose and tumors suggest the possible evolutionary origin of mammalian adipose from some ancestral benign mesenchymal hereditary tumors. Indeed, using a transgenic inducible zebrafish tumor model, we described many genes, which originated in fish and were expressed in fish tumors. Their human orthologs LEP, NOTCH1, SPRY1, PPARG, ID2, and CIDEA acquired functions connected with the adipose organ. They are also involved in tumor development in humans. Conclusion If the hypothesis of the evolutionary origin of the adipose organ from the ancestral hereditary tumor is correct, it may open new opportunities to resolve the oncological problem and the problem of the obesity epidemic. New interventions targeting LEP, NOTCH1, SPRY1, PPARG, ID2, and CIDEA gene network, in addition to what already is going on, can be designed for treatment and prevention of both obesity and tumors.

The Theory of Carcino-Evo-Devo and Its Non-Trivial Predictions

“…The important non-trivial prediction of the main hypothesis that evolutionarily new genes should be specifically expressed in tumors is contained in the formulation of the hypothesis. This prediction has been addressed in many of our papers [ 10 , 15 , 20 , 21 , 22 , 23 , 24 , 25 , 26 , 27 , 28 , 29 , 30 , 31 , 32 , 33 , 34 , 35 , 36 , 37 ].…”

“…The author addressed this topic in the book [ 9 ] and in two recently published papers devoted solely to this question [ 12 , 13 ]. In [ 12 ], the author was looking for tumor features of four mammalian evolutionarily novel organs: placenta, mammary gland, prostate and infantile human brain.…”

“…In [ 12 ], the author was looking for tumor features of four mammalian evolutionarily novel organs: placenta, mammary gland, prostate and infantile human brain. In [ 13 ], the tumor-like features of mammalian adipose were described for the first time in the literature, a discovery that can change the medicine of obesity and cancer.…”

“…Since then, the concept of the positive evolutionary role of tumors has been developed in a series of publications [ 3 , 4 , 5 , 6 , 7 , 8 ]. In the book Evolution by Tumor Neofunctionalization [ 9 ], with its twelve chapters and over one thousand references, this concept started to gain the shape of the theory, which was further developed in subsequent publications [ 10 , 11 , 12 , 13 , 14 ]. In a 2019 paper, the author called this new theory the “ carcino-evo-devo ” theory to stress the role of heritable tumors in the evolution of development [ 11 ].…”

Polyploidy and Myc Proto-Oncogenes Promote Stress Adaptation via Epigenetic Plasticity and Gene Regulatory Network Rewiring

“…Recent phylostratigraphic data indicate that both polyploidy and Myc shift the expression of genes toward unicellularity [ 43 , 73 ]. Polyploidy-associated features of stemness and metabostemness are also observed in unicellular primitive organisms, further confirming that polyploidy promotes dedifferentiation and primitive ancient traits, including the activation of ancestral gene modules related to glycolysis, epithelial-to-mesenchymal transition, housekeeping genes, cell cycle, ribosome biogenesis, and flexible adaptive reaction to stress [ 22 , 190 , 191 , 192 , 193 , 194 , 195 , 196 ]. The connection between polyploidy and unicellularity is not surprising because polyploidy is an ancient phenomenon that appeared together with reproductive cysts of unicellular organisms [ 197 ].…”