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Transmembrane voltage potential is an essential cellular parameter for the detection and control of tumor development in a Xenopus model

Understanding mechanisms that orchestrate cell behavior into appropriately patterned tissues and organs within the organism is an essential element of preventing, detecting and treating cancer. Bioelectric signals (resting transmembrane voltage potential gradients in all cells) underlie an important...

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Autores principales: Chernet, Brook T., Levin, Michael
Formato: Online Artículo Texto
Lenguaje:English
Publicado: The Company of Biologists Limited 2013
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3634644/
https://www.ncbi.nlm.nih.gov/pubmed/23471912
http://dx.doi.org/10.1242/dmm.010835
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author Chernet, Brook T.
Levin, Michael
author_facet Chernet, Brook T.
Levin, Michael
author_sort Chernet, Brook T.
collection PubMed
description Understanding mechanisms that orchestrate cell behavior into appropriately patterned tissues and organs within the organism is an essential element of preventing, detecting and treating cancer. Bioelectric signals (resting transmembrane voltage potential gradients in all cells) underlie an important and broadly conserved set of control mechanisms that regulate pattern formation. We tested the role of transmembrane potential in tumorigenesis mediated by canonical oncogenes in Xenopus laevis. Depolarized membrane potential (V(mem)) was a characteristic of induced tumor-like structures (ITLSs) generated by overexpression of Gli1, Kras(G12D), Xrel3 or p53(Trp248). This bioelectric signature was also present in precursor ITLS sites. V(mem) is a bioelectric marker that reveals ITLSs before they become histologically and morphologically apparent. Moreover, voltage was functionally important: overexpression of hyperpolarizing ion transporters caused a return to normal V(mem) and significantly reduced ITLS formation in vivo. To characterize the molecular mechanism by which V(mem) change regulates ITLS phenotypes, we performed a suppression screen. V(mem) hyperpolarization was transduced into downstream events via V(mem)-regulated activity of SLC5A8, a sodium-butyrate exchanger previously implicated in human cancer. These data indicate that butyrate, a histone deacetylase (HDAC) inhibitor, might be responsible for transcriptional events that mediate suppression of ITLSs by hyperpolarization. V(mem) is a convenient cellular parameter by which tumors induced by human oncogenes can be detected in vivo and represents a new diagnostic modality. Moreover, control of resting membrane potential is functionally involved in the process by which oncogene-bearing cells depart from normal morphogenesis programs to form tumors. Modulation of V(mem) levels is a novel and promising strategy for tumor normalization.
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spelling pubmed-36346442013-06-19 Transmembrane voltage potential is an essential cellular parameter for the detection and control of tumor development in a Xenopus model Chernet, Brook T. Levin, Michael Dis Model Mech Research Article Understanding mechanisms that orchestrate cell behavior into appropriately patterned tissues and organs within the organism is an essential element of preventing, detecting and treating cancer. Bioelectric signals (resting transmembrane voltage potential gradients in all cells) underlie an important and broadly conserved set of control mechanisms that regulate pattern formation. We tested the role of transmembrane potential in tumorigenesis mediated by canonical oncogenes in Xenopus laevis. Depolarized membrane potential (V(mem)) was a characteristic of induced tumor-like structures (ITLSs) generated by overexpression of Gli1, Kras(G12D), Xrel3 or p53(Trp248). This bioelectric signature was also present in precursor ITLS sites. V(mem) is a bioelectric marker that reveals ITLSs before they become histologically and morphologically apparent. Moreover, voltage was functionally important: overexpression of hyperpolarizing ion transporters caused a return to normal V(mem) and significantly reduced ITLS formation in vivo. To characterize the molecular mechanism by which V(mem) change regulates ITLS phenotypes, we performed a suppression screen. V(mem) hyperpolarization was transduced into downstream events via V(mem)-regulated activity of SLC5A8, a sodium-butyrate exchanger previously implicated in human cancer. These data indicate that butyrate, a histone deacetylase (HDAC) inhibitor, might be responsible for transcriptional events that mediate suppression of ITLSs by hyperpolarization. V(mem) is a convenient cellular parameter by which tumors induced by human oncogenes can be detected in vivo and represents a new diagnostic modality. Moreover, control of resting membrane potential is functionally involved in the process by which oncogene-bearing cells depart from normal morphogenesis programs to form tumors. Modulation of V(mem) levels is a novel and promising strategy for tumor normalization. The Company of Biologists Limited 2013-05 2013-02-01 /pmc/articles/PMC3634644/ /pubmed/23471912 http://dx.doi.org/10.1242/dmm.010835 Text en © 2013. Published by The Company of Biologists Ltd This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial Share Alike License (http://creativecommons.org/licenses/by-nc-sa/3.0), which permits unrestricted non-commercial use, distribution and reproduction in any medium provided that the original work is properly cited and all further distributions of the work or adaptation are subject to the same Creative Commons License terms.
spellingShingle Research Article
Chernet, Brook T.
Levin, Michael
Transmembrane voltage potential is an essential cellular parameter for the detection and control of tumor development in a Xenopus model
title Transmembrane voltage potential is an essential cellular parameter for the detection and control of tumor development in a Xenopus model
title_full Transmembrane voltage potential is an essential cellular parameter for the detection and control of tumor development in a Xenopus model
title_fullStr Transmembrane voltage potential is an essential cellular parameter for the detection and control of tumor development in a Xenopus model
title_full_unstemmed Transmembrane voltage potential is an essential cellular parameter for the detection and control of tumor development in a Xenopus model
title_short Transmembrane voltage potential is an essential cellular parameter for the detection and control of tumor development in a Xenopus model
title_sort transmembrane voltage potential is an essential cellular parameter for the detection and control of tumor development in a xenopus model
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3634644/
https://www.ncbi.nlm.nih.gov/pubmed/23471912
http://dx.doi.org/10.1242/dmm.010835
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