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Israël. J Cancer Metastasis Treat 2019;5:12 Journal of Cancer
DOI: 10.20517/2394-4722.2018.78 Metastasis and Treatment

Review Open Access

Metabolic rewiring of stem cells and differentiated
cells in cancer: the hypothetical consequences of a

GABA deficiency in endocrine pancreas

Maurice Israël

Institut Alfred Fessard, Centre National de la Recherche Scientifique, 2 Av. Terrasse, 91190 Gif sur Yvette, France.

Correspondence to: Dr. Maurice Israël, Institut Alfred Fessard, Centre National de la Recherche Scientifique, 2 Av. Aristide
Briand, 91440 Bures sur Yvette, France. E-mail: mauisrael@wanadoo.fr

How to cite this article: Israël M. Metabolic rewiring of stem cells and differentiated cells in cancer: the hypothetical consequences
of a GABA deficiency in endocrine pancreas. J Cancer Metastasis Treat 2019;5:12.
http://dx.doi.org/10.20517/2394-4722.2018.78

Received: 22 Nov 2018 First Decision: 21 Dec 2018 Revised: 14 Jan 2019 Accepted: 16 Jan 2019 Published: 27 Feb 2019

Science Editor: Rafat Siddiqui Copy Editor: Cai-Hong Wang Production Editor: Huan-Liang Wu

Abstract
The carcinogenic mechanism proposed considers that stem cells committed to repair tissues and differentiated
cells, acquire different metabolic properties, if there is an associated GABA deficiency suppressing a control
system of the endocrine pancreas. This control system mediated by GABA, released with insulin, normally turns off
glucagon and somatostatin release when insulin is released. A consequence of the GABA deficiency in pancreas
and adrenals is a hybrid insulin-glucagon-somatostatin message, received by new mitotic stem cells displaying
then a hybrid metabolic rewiring. This gives them a selective metabolic advantage over differentiated cells that
become insulin resistant and only receive the glucagon- somatostatin part of the hormonal message. Indeed, their
insulin receptors are desensitized by the persistent leakage of insulin resulting from the GABA deficiency that fails
to close the insulin release mechanism. Thus differentiated cells are simply rewired to be plundered by stem cells.
The metabolic advantage gained by stem cells blocks their own differentiation and maintains their mitotic capacity.
Inevitable mutations of mitotic cells follow, the immune system is unable to eliminate a geometrically increasing
number of altered stem cells, a selection of the most aggressive but metabolically successful population takes place
when cancer is declared.

© The Author(s) 2019. Open Access This article is licensed under a Creative Commons Attribution 4.0
International License (https://creativecommons.org/licenses/by/4.0/), which permits unrestricted use,
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