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J Med Oncl Ther 2017 | Volume 2 Issue 4
allied
academies
Oncology and Biomarkers Summit
November 27-28, 2017 | Atlanta, USA
Annual Congress on
O
verhydration of cells is a hallmark for early detection of
cancer. However, the nature of the metabolic mechanism,
the dysfunction of which leads to decontrolling of cell hydration
and generation of Warburg phenomena in cancer cells, has
not been elucidated yet. Na
+
/K
+
-ATPase, having a central role
in metabolic regulation of cell hydration, has three catalytic
isoforms with different affinities to ouabain and functional
activities.Amongtheseisoforms,theα3isoform,withthehighest
affinity to ouabain, isn’t involved in ion-transporting process
and has an intracellular signaling function. It is known that α3
isoforms of Na
+
/K
+
-ATPase, which are absent in non-excitable
cells of healthy animals, are highly expressed in cancerous cells.
Based on this, the expression of these isoforms is considered as
one of the early hallmarks for carcinogenesis. However, by our
previous work it has been shown that all 3 isoforms are present
both in tumor and non-excitable tissues of mice carrying
sarcoma-180. It has also been shown that α3 isoform, which is
absent in non-excitable cells of healthy animals, appears in non-
cancerous tissues of women with breast cancer, as well as in
all non-excitable tissues of mice carrying sarcoma-180 tumor.
Moreover, it has also been shown that this expression of α3
isoform is accompanied by cell hydration. Based on these data,
it has been hypothesized that the dysfunction of intracellular
signaling system controlling cell hydration could serve as a
primarymechanismfor carcinogenesis. Tocheck thishypothesis,
in non-excitable tissues of healthy and sarcoma-180 carrying
mice (including tumor tissues), dose-dependent ouabain
effects on Na
+
/K
+
-pump activity, cell hydration, intracellular
cyclic nucleotides (cGMP and cAMP), glycolysis rate (lactate
concentration in blood and lactate dehydrogenase activity),
membrane permeability for protons, Na
+
/H
+
, Na
+
/Ca
2+
exchange
and cell proliferation by means of electrophysiological, isotope,
immunoassay and microscopic methods were studied. These
studies have brought us to conclusion that the dysfunction
of α3 isoform-dependent cGMP-activated Na
+
/Ca
2+
exchange
in forward mode, which controls Na
+
/K
+
-pump activity, cell
hydration, membrane permeability for Na
+
and Ca
2+
, glycolysis
activity and cell proliferation, is a primary mechanism for
generation of cell overhydration and Warburg phenomena
leading to carcinogenesis. Therefore, α3 isoform-dependent
cGMP-activated Na
+
/Ca
2+
exchange in forward mode has been
suggested as a novel therapeutic target for early stage of
carcinogenesis.
Speaker Biography
Vagharsh Khachikyan has received his PhD in Cancer Therapy at Yerevan State Medical
University. Currently, he is a Physician at National Center of Oncology named after V
A Fanarjyan and a Senior Scientist and Lecturer at UNESCO Chair in Life Sciences at
Life Sciences International Postgraduate Educational Center. He also conducts lectures
on oncology at UNESCO Chair in Life Sciences. His research includes the study of the
dysfunction of intracellular signaling system responsible for cancer generation. He has
participated in many international trainings and conferences.
e:
info@biophys.amVagharsh Khachikyan
Life Sciences International Postgraduate Educational Center, Armenia
The dysfunction of cGMP-activated Na
+
/Ca
2+
exchange controlling cell
hydration is a primary mechanism for carcinogenesis