The H<sup>+</sup>Vacuolar ATPase Maintains Neural Stem Cells in the Developing Mouse Cortex

Lange, Christian; Prenninger, Silvia; Knuckles, Philip; Taylor, Verdon; Levin, Michael; Calegari, Federico

doi:10.1089/scd.2010.0484

Cited by 77 publications

(57 citation statements)

References 51 publications

(83 reference statements)

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“…This cleavage defect upon V-ATPase inhibition could be due to the dependence of ␥-secretase on an acidic environment to cleave the Notch receptor, or it could be that the acidic pH generated by the V-ATPase serves to activate cofactors that stimulate cleavage. Similar effects were also observed in normal and transformed human cell lines, as well as during mouse development (86,92,178,198). In Notch-addicted breast tumor cell lines, V-ATPase inhibition reduced cell proliferation (86).…”

Section: V-atpase and Notch Signalingsupporting

confidence: 57%

The Function of V-ATPases in Cancer

Stransky

Cotter

Forgac

2016

Physiological Reviews

236

268

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The vacuolar ATPases (V-ATPases) are a family of proton pumps that couple ATP hydrolysis to proton transport into intracellular compartments and across the plasma membrane. They function in a wide array of normal cellular processes, including membrane traffic, protein processing and degradation, and the coupled transport of small molecules, as well as such physiological processes as urinary acidification and bone resorption. The V-ATPases have also been implicated in a number of disease processes, including viral infection, renal disease, and bone resorption defects. This review is focused on the growing evidence for the important role of V-ATPases in cancer. This includes functions in cellular signaling (particularly Wnt, Notch, and mTOR signaling), cancer cell survival in the highly acidic environment of tumors, aiding the development of drug resistance, as well as crucial roles in tumor cell invasion, migration, and metastasis. Of greatest excitement is evidence that at least some tumors express isoforms of V-ATPase subunits whose disruption is not lethal, leading to the possibility of developing anti-cancer therapeutics that selectively target V-ATPases that function in cancer cells.

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Section: V-atpase and Notch Signalingsupporting

confidence: 57%

The Function of V-ATPases in Cancer

Stransky

Cotter

Forgac

2016

Physiological Reviews

236

268

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“…stem cells), while differentiation is caused by increase of negative V mem [215]. Functional control of cell state by changes in V mem has been observed in many kinds of stem and progenitor cells [216][217][218][219][220][221][222][223][224][225][226], including adult human mesenchymal stem cells [222,227], which can be kept stem-like despite the presence of chemical differentiation factors by forced depolarization, and in induced pluripotent stem cells [228]. Even mature CNS neurons can be made to re-enter mitosis by sustained depolarization [229,230], revealing the power of transmembrane potential to regulate proliferative potential in adult somatic cells.…”

Section: Bioelectric States Control Cell Behaviormentioning

confidence: 99%

Cancer as a disorder of patterning information: computational and biophysical perspectives on the cancer problem

Moore

Walker

Levin

2017

Converg. Sci. Phys. Oncol.

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TOPICAL REVIEWCancer as a disorder of patterning information: computational and biophysical perspectives on the cancer problem IntroductionCancer is well-recognized not only as an extremely pernicious medical problem, but also as a group of phenomena deeply connected to the fundamental questions of evolution, multicellularity, pattern (disregulation, and the interplay between the genome and the environment [1,2]. Two fundamental paradigms currently divide the field. One is that cancer results from disorders of genetics: cancer cells are fundamentally broken due to genomic mutation or instability, and their clonal progeny form tumors and metastases. This view is sometimes called the SMT, somatic mutation theory [3][4][5]. A competing perspective is that of cancer as a circuit disease-a disorder of the complex biophysical, transcriptional, and epigenetic dynamics that regulate cellular state and the ability of cells to cooperate in vivo [6][7][8]. Under this view (sometimes called the tissue organization field theory or TOFT, [9,10]), cancer is akin to a traffic jam [11]-the problem is not a permanent discrete alteration within a founder cell and all of its clonal descendants, but an undesirable stable attractor in the complex network of controls that normally guides anatomical homeostasis [12].The relative merits of the two models have been discussed extensively [10,[13][14][15][16][17] AbstractThe current paradigm views cancer as arising clonally from a degradation of genetic information in single cells. A complementary perspective, originating at the dawn of modern developmental biology, is that cancer is the result of a system disorder of algorithms that normally orchestrate individual cell activities toward specific anatomical structures and away from tumorigenesis. A view of cancer as a disease of geometry focuses on the pathways that allow cells to cooperate to build and maintain large-scale anatomical patterning. Cancer may result when cells stop maintaining higher-order structures and reduce the boundary of their computational selves to a single-cell level, reverting to a unicellular lifestyle in which the rest of the organism is merely part of the environment at the expense of which all living things survive. While this view has been widely discussed, little progress has been made in providing a quantitative, mechanistic framework within which this perspective's specific and unique implications for treatment strategies can be tested and biomedically exploited. Here, we highlight two recent areas of progress which may facilitate much-needed progress on the cancer problem. First, we review the roles that endogenous bioelectrical networks, operating across many tissues in vivo, play as a medium of information processing in tumor suppression, progression, and reprogramming. Second, we provide a primer to the development of computational theory and tools for quantifying the information and causal control structures in cancer and other complex biological systems. Rigorous mathematical formalisms now exist to...

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“…In normal development, embryonic stem cells gradually progress from a multipotent state, capable of generating all cell types, to a highly restricted state by sequential restriction of differentiation potential (Chambers and Studer, 2011). These differentiation processes have been shown to be subject to manipulation from various signaling cues, such as transcription factor expression (Mong et al, 2014, Weintraub et al, 1989 but have also been shown to be directed by bioelectrical events (Barth and Barth, 1974, Lange et al, 2011, Sundelacruz et al, 2009. While much of this work has been done in vitro, our data suggest that in vivo depolarization can also affect cell fate determination.…”

Section: D'mentioning

confidence: 99%

Selective depolarization of transmembrane potential alters muscle patterning and muscle cell localization in Xenopus laevis embryos

Lobikin

Paré²,

Kaplan³

et al. 2015

Int. J. Dev. Biol.

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The correct anatomical placement and precise determination of specific cell types is required for the establishment of normal embryonic patterning. Understanding these processes is also important for progress in regenerative medicine and cancer biology. Transmembrane voltage gradients across embryonic tissues can mediate cellular communication to regulate the processes of proliferation, migration, and differentiation. Our past work showed that selective depolarization of an endogenous instructor cell population in Xenopus laevis in vivo induced a melanoma-like phenotype in the absence of genetic damage. Here, we use a hypersensitive glycine-gated chloride channel (GlyR) under control of tissue-specific promoters to show that instructor cells resident within muscle are more effective at triggering the metastatic conversion of ectodermal melanocytes than those similar cells within the nervous system. Moreover, depolarization of muscle cells results in aberrant muscle patterning and the appearance of cells expressing muscle markers within the neural tube, which impacts but does not abolish the animals' ability to learn in an associative conditioning assay. Taken together, our data reveal new details of long-range (non-cell-autonomous) reprogramming of cell behavior via alteration of the resting potential of specific embryonic subpopulations.

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The H⁺Vacuolar ATPase Maintains Neural Stem Cells in the Developing Mouse Cortex

Cited by 77 publications

References 51 publications

The Function of V-ATPases in Cancer

The Function of V-ATPases in Cancer

Cancer as a disorder of patterning information: computational and biophysical perspectives on the cancer problem

Selective depolarization of transmembrane potential alters muscle patterning and muscle cell localization in Xenopus laevis embryos

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The H+Vacuolar ATPase Maintains Neural Stem Cells in the Developing Mouse Cortex

Cited by 77 publications

References 51 publications

The Function of V-ATPases in Cancer

The Function of V-ATPases in Cancer

Cancer as a disorder of patterning information: computational and biophysical perspectives on the cancer problem

Selective depolarization of transmembrane potential alters muscle patterning and muscle cell localization in Xenopus laevis embryos

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The H⁺Vacuolar ATPase Maintains Neural Stem Cells in the Developing Mouse Cortex