Evolution of energy metabolism, stem cells and cancer stem cells: how the warburg and barker hypotheses might be linked - PubMed (original) (raw)

Evolution of energy metabolism, stem cells and cancer stem cells: how the warburg and barker hypotheses might be linked

James E Trosko et al. Int J Stem Cells. 2012 May.

Abstract

The evolutionary transition from single cells to the metazoan forced the appearance of adult stem cells and a hypoxic niche, when oxygenation of the environment forced the appearance of oxidative phosphorylation from that of glycolysis. The prevailing paradigm in the cancer field is that cancers start from the "immortalization" or "re-programming" of a normal, differentiated cell with many mitochondria, that metabolize via oxidative phosphorylation. This paradigm has been challenged with one that assumes that the target cell for carcinogenesis is the normal, immortal adult stem cell, with few mitochondria. This adult organ-specific stem cell is blocked from "mortalizing" or from "programming" to be terminally differentiated. Two hypotheses have been offered to explain cancers, namely, the "stem cell theory" and the "de-differentiation" or "re-programming" theory. This Commentary postulates that the paleochemistry of the oceans, which, initially, provided conditions for life' s energy to arise via glycolysis, changed to oxidative phosphorylation for life' s processes. In doing so, stem cells evolved, within hypoxic niches, to protect the species germinal and somatic genomes. This Commentary provides support for the "stem cell theory", in that cancer cells, which, unlike differentiated cells, have few mitochondria and metabolize via glycolysis. The major argument against the "de-differentiation theory" is that, if re-programming of a differentiated cell to an "induced pluri-potent stem cell" happened in an adult, teratomas, rather than carcinomas, should be the result.

Keywords: Adult; Cancer; Carcinogenesis; Stem cells.

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Figures

Fig. 1.

Fig. 1.. These diagrams illustrate two possible means by which stem cells (Oct-4 +) decide to divide by symmetrical or asymmetrical division. In panel A, if a stem cell binds to a specific extracellular matrix, as symbolized by attaching to a coated plastic dish, the signal received combines with signals in the medium (growth factors, Ca++, nutrients, oxygen, etc.) to stimulate genes and gene products to bring about the division plane to be perpendicular to the attachment plane. As a result, both daughter cells continue to have identical signaling as did the maternal stem cell (symmetrical cell division or expansion of the stem cell population). In panel B, the stem cell binds to a different substrate molecule, as represented by a natural extra-cellular molecule, such as laminin or collagen type 4. In this case, the signal this substrate molecule induces a different intracellular signal that interacts with the same signals from the medium, Ca++, oxygen, etc. to stimulate different genes and gene products to cause a division plane within the stem cell to be formed parallel to the attachment plane. In this case, the daughter cell on the bottom will mimic the same intracellular signaling as its maternal stem cell. Important to note that if these stem cells do not have functional gap junctional intercellular communication, then these signals are not transmitted to the other daughter cell because that daughter cell does not interact with the substrate signal. As a result, these daughter cells receive a different set of combined signals that trigger a commitment to become a progenitor and ultimately terminally differentiated progeny (Permission granted from Oxford University Press, 2011).

Fig. 2.

Fig. 2.. Filamentation of aerobically grown Hpx-mutants of E. coli cells. Cells were grown in Luria broth, anaerobically (A) or aerobically (B). Magnification: × 400. Permission granted by PNAS .

Fig. 3.

Fig. 3.. E.coli, grown in traditional growth medium, showing normal morphology. However, when E.coli were grown in the same medium but with a submerged platinum electrode, the E.coli had their DNA replicate but they did not septate. This observation led to Dr. Barnett Rosenberg’ s discovery of the anti-cancer drug, cis-platin. Permission grant by: Paul Rosenberg of the Board of Barros Foundation.

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