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Membrane-Depolarizi...
Membrane-Depolarizing Channel Blockers Induce Selective Glioma Cell Death by Impairing Nutrient Transport and Unfolded Protein/Amino Acid Responses
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- Niklasson, Mia (author)
- Uppsala universitet,Science for Life Laboratory, SciLifeLab,Neuroonkologi
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Maddalo, Gianluca (author)
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Sramkova, Zuzana (author)
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Mutlu, Ercan (author)
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Wee, Shimei (author)
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Sekyrova, Petra (author)
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- Schmidt, Linnea (author)
- Uppsala universitet,Neuroonkologi,Science for Life Laboratory, SciLifeLab
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- Fritz, Nicolas (author)
- Karolinska Institutet,KTH,Science for Life Laboratory, SciLifeLab
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- Dehnisch, Ivar (author)
- Karolinska Institutet
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Kyriatzis, Gregorios (author)
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Krafcikova, Michaela (author)
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Carson, Brittany B. (author)
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Feenstra, Jennifer M. (author)
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- Marinescu, Voichita (author)
- Uppsala universitet,Science for Life Laboratory, SciLifeLab,Medicinsk genetik och genomik
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- Segerman, Anna (author)
- Uppsala universitet,Neuroonkologi,Science for Life Laboratory, SciLifeLab
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- Haraldsson, Martin (author)
- Karolinska Institutet
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- Gustavsson, Anna-Lena (author)
- Karolinska Institutet
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Hammarstrom, Lars G. J. (author)
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- Jensen, Annika Jenmalm (author)
- Karolinska Institutet
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- Uhrbom, Lene (author)
- Uppsala universitet,Neuroonkologi,Science for Life Laboratory, SciLifeLab
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- Altelaar, A. F. Maarten (author)
- Karolinska Institutet
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- Linnarsson, Sten (author)
- Karolinska Institutet
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- Uhlen, Per (author)
- Karolinska Institutet
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Trantirek, Lukas (author)
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Vincent, C. Theresa (author)
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- Nelander, Sven (author)
- Uppsala universitet,Neuroonkologi,Science for Life Laboratory, SciLifeLab
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Enger, Per Oyvind (author)
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Andang, Michael (author)
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(creator_code:org_t)
- AMER ASSOC CANCER RESEARCH, 2017
- 2017
- English.
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In: Cancer Research. - : AMER ASSOC CANCER RESEARCH. - 0008-5472 .- 1538-7445. ; 77:7, s. 1741-1752
- Related links:
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https://urn.kb.se/re...
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https://doi.org/10.1...
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https://urn.kb.se/re...
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http://kipublication...
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Abstract
Subject headings
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- Glioma-initiating cells (GIC) are considered the underlying cause of recurrences of aggressive glioblastomas, replenishing the tumor population and undermining the efficacy of conventional chemotherapy. Here we report the discovery that inhibiting T-type voltage-gated Ca2+ and KCa channels can effectively induce selective cell death of GIC and increase host survival in an orthotopic mouse model of human glioma. At present, the precise cellular pathways affected by the drugs affecting these channels are unknown. However, using cell-based assays and integrated proteomics, phosphoproteomics, and transcriptomics analyses, we identified the downstreamsignaling events these drugs affect. Changes in plasma membrane depolarization and elevated intracellular Na+, which compromised Na+-dependent nutrient transport, were documented. Deficits in nutrient deficit acted in turn to trigger the unfolded protein response and the amino acid response, leading ultimately to nutrient starvation and GIC cell death. Our results suggest new therapeutic targets to attack aggressive gliomas.
Subject headings
- MEDICIN OCH HÄLSOVETENSKAP -- Medicinsk bioteknologi -- Medicinsk bioteknologi (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Medical Biotechnology -- Medical Biotechnology (hsv//eng)
- MEDICIN OCH HÄLSOVETENSKAP -- Klinisk medicin -- Cancer och onkologi (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Clinical Medicine -- Cancer and Oncology (hsv//eng)
Publication and Content Type
- ref (subject category)
- art (subject category)
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To the university's database
- By the author/editor
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Niklasson, Mia
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Maddalo, Gianluc ...
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Sramkova, Zuzana
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Mutlu, Ercan
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Wee, Shimei
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Sekyrova, Petra
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show more...
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Schmidt, Linnea
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Fritz, Nicolas
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Dehnisch, Ivar
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Kyriatzis, Grego ...
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Krafcikova, Mich ...
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Carson, Brittany ...
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Feenstra, Jennif ...
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Marinescu, Voich ...
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Segerman, Anna
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Haraldsson, Mart ...
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Gustavsson, Anna ...
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Hammarstrom, Lar ...
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Jensen, Annika J ...
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Uhrbom, Lene
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Altelaar, A. F. ...
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Linnarsson, Sten
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Uhlen, Per
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Trantirek, Lukas
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Vincent, C. Ther ...
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Nelander, Sven
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Enger, Per Oyvin ...
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Andang, Michael
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show less...
- About the subject
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- MEDICAL AND HEALTH SCIENCES
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MEDICAL AND HEAL ...
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and Medical Biotechn ...
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and Medical Biotechn ...
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- MEDICAL AND HEALTH SCIENCES
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MEDICAL AND HEAL ...
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and Clinical Medicin ...
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and Cancer and Oncol ...
- Articles in the publication
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Cancer Research
- By the university
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Royal Institute of Technology
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Uppsala University
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Karolinska Institutet