Carcinogenesis and the plasma membrane

Presented is a two-stage hypothesis of carcinogenesis based on: (1) plasma membrane defects that produce abnormal electron and proton efflux; and (2) electrical uncoupling of cells through loss of intercellular communication. These changes can be induced by a wide variety of stimuli including chemic...

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Bibliographic Details
Published in:Medical hypotheses 1999-05, Vol.52 (5), p.367-372
Main Authors: Stern, R.G., Milestone, B.N., Gatenby, R.A.
Format: Article
Language:English
Subjects:
Animals
Biological and medical sciences
Carcinogenesis, carcinogens and anticarcinogens
Carcinogens - toxicity
Cell Communication
Cell Membrane - drug effects
Cell Membrane - physiology
Cell Transformation, Neoplastic
General aspects
Humans
Medical sciences
Models, Biological
Neoplasms - pathology
Neoplasms - physiopathology
Tumors
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Summary:Presented is a two-stage hypothesis of carcinogenesis based on: (1) plasma membrane defects that produce abnormal electron and proton efflux; and (2) electrical uncoupling of cells through loss of intercellular communication. These changes can be induced by a wide variety of stimuli including chemical carcinogens, oncoviruses, inherited and/or acquired genetic defects, and epigenetic abnormalities. The resulting loss of electron/proton homeostasis leads to decreased transmembrane potential, electrical microenvironment alterations, decreased extracellular pH, and increased intracellular pH. This produces a positive feedback loop to enhance and sustain the proton/electron efflux and loss of intercellular communication. Low transmembrane potential is functionally related to rapid cell cycling, changes in membrane structure, and malignancy. Intracellular alkalinization affects a variety of pH-sensitive systems including glycolysis, DNA synthesis, DNA transcription and DNA repair, and promotes genetic instability, accounting for the accumulation of genetic defects seen in malignancy. The abnormal microenvironment results in the selective survival and proliferation of malignant cells at the expense of contiguous normal cell populations.
ISSN:0306-9877
1532-2777
DOI:10.1054/mehy.1997.0657