If not, should there be? When we look upstream from genes, we are confronted with our personally unique 'elementome'. Cancer as a mitochondrial metabolic disease (2015 Seyfried ) considers environment but focuses on one organelle. While it is hard to argue the great science behind SMT, TOFL (Sonneschein& Soto), Bissel's stromal related studies, and Seyfried above...but they all seem downstream in that they fail to mention, downplay the environment, or key on specific micro env. The way I see it, it seems highly unlikely a single organelle/compartment in a cell is responsible for the root cause. Thoughts?
It is established that the dysfunction of Na+/K+-pump is a common consequence of any pathology, including cancer. At the same time, it is also known that among a number of mechanisms involved in cell volume regulation, Na+/K+-pump has a central role in it. This role of pump is due to its two important properties: a) Na+/K+-pump which generates Na+ gradient on the membrane serves as an energy source for a number of secondary ionic transporters, such as, Na+/Ca2+, Na+/H+, Na+/sugars, amino acids & other osmolytes and b) Na+/K+-pump, having the highest metabolic energy (ATP) utilizing mechanism, has a great intracellular signaling role in regulation of sorption properties of intracellular structure as well as in generation of water molecules during oxidative glucose processes in cells. Na+/K+-ATPase (working molecules of Na+/K+-pump) has 4 catalytic subunits having different functional activities and sensitivities to cardiac glycoside: α1 (low), α2 (middle), α3 and α4 (high), the latter is identified only in testis. From these isoforms α1 (fully) and α2 (partly) have ion transporting functions, while α3 isoform only performs intracellular signaling function. By previous our study it was shown that dysfunction of α3 isoform-dependent signaling function controlling cell hydration stimulates carcinogenesis: So its information for thinking.
Thanks Karen Had looked at this aspect through RJP Williams + Frausto da Silva and a little from Sabeeha Merchant. Sure does seem to be a connection.
Am intrigued by your use (a common one) of the word 'dysfunction' regarding a cell pathway/system like Na+/K+ pump. Could it actually be a normal response to the present cellular conditions/environment the cell is under...perhaps a pH reversal, and or surpluses or deficiencies of certain elements? Science is based so much on cells behaving predictably in a given environment stressed by 'X" condition...
Bioenergetic theory of Carcinogenesis
https://www.researchgate.net/publication/229325765_The_bio-energetic_theory_of_carcinogenesis
Article The bio-energetic theory of carcinogenesis
Very interesting question! I believe the Bioenergetic Theory of Carcinogenesis may provide some substance to this formidable concept.
Dr Gonzalez: Very much appreciated! I found a heavily highlighted version of your paper in an archive which I previously reviewed in 2013. It was great to undertake a follow-up review of it today and see aspects of changes in the Na/K pump Karen D also notes above. I also think your paper highlights (and speaks directly to) a # of the downstream cellular expressions observed in cancer, particularly the result of a 60% reduction in available O2. Am trying to relate that understanding in the context of a mole rat/low oxygen env and very low cancer rates (such a variable disease!) Will continue to search for elemental surplus, deficiency, and/or toxic profiles...or put another way, do cell's function in a consistent manner when possessing similar chemical profiles under similar pHe/pHi. In junior high-school we preach this is the very foundation for experimental science...this fundamental principal just seems lost in the sophistication hype we more often see. Perhaps science doesn't routinely measure elemental profiles to this fidelity and precision and within such a dynamic environment yet...but the larger community sure brags about the proteome and metabolome contribution they fail to 1st appreciate and then incorporate the linked 'omic' disciplines.
Excellent and relevant follow up to a paradigm changing concept. Fresh ideas are much appreciated and needed to improve current therapeutic outcomes.
I greatly appreciate the encouragement. If interested, here is a link to our website with a process drawing of 'from what we are created' http://www.stressingcancer.com/wp-content/uploads/2012/04/Slide13-e1441676332877.jpg
we continue to see more research that supports our 'one/singular cause' of cancer theory. we recently updated our homepage to our website www.stressingcancer.com would be interested in your thoughts
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