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  • Niklasson, MiaUppsala universitet,Science for Life Laboratory, SciLifeLab,Neuroonkologi (author)

Membrane-Depolarizing Channel Blockers Induce Selective Glioma Cell Death by Impairing Nutrient Transport and Unfolded Protein/Amino Acid Responses

  • Article/chapterEnglish2017

Publisher, publication year, extent ...

  • AMER ASSOC CANCER RESEARCH,2017
  • printrdacarrier

Numbers

  • LIBRIS-ID:oai:DiVA.org:kth-205434
  • https://urn.kb.se/resolve?urn=urn:nbn:se:kth:diva-205434URI
  • https://doi.org/10.1158/0008-5472.CAN-16-2274DOI
  • https://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-318377URI
  • http://kipublications.ki.se/Default.aspx?queryparsed=id:135475747URI

Supplementary language notes

  • Language:English
  • Summary in:English

Part of subdatabase

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  • Subject category:ref swepub-contenttype
  • Subject category:art swepub-publicationtype

Notes

  • QC 20170522
  • 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.

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Added entries (persons, corporate bodies, meetings, titles ...)

  • Maddalo, Gianluca (author)
  • Sramkova, Zuzana (author)
  • Mutlu, Ercan (author)
  • Wee, Shimei (author)
  • Sekyrova, Petra (author)
  • Schmidt, LinneaUppsala universitet,Neuroonkologi,Science for Life Laboratory, SciLifeLab(Swepub:uu)linsc345 (author)
  • Fritz, NicolasKarolinska Institutet,KTH,Science for Life Laboratory, SciLifeLab(Swepub:kth)u19ttapk (author)
  • Dehnisch, IvarKarolinska Institutet (author)
  • Kyriatzis, Gregorios (author)
  • Krafcikova, Michaela (author)
  • Carson, Brittany B. (author)
  • Feenstra, Jennifer M. (author)
  • Marinescu, VoichitaUppsala universitet,Science for Life Laboratory, SciLifeLab,Medicinsk genetik och genomik(Swepub:uu)voima415 (author)
  • Segerman, AnnaUppsala universitet,Neuroonkologi,Science for Life Laboratory, SciLifeLab(Swepub:uu)annse483 (author)
  • Haraldsson, MartinKarolinska Institutet (author)
  • Gustavsson, Anna-LenaKarolinska Institutet (author)
  • Hammarstrom, Lars G. J. (author)
  • Jensen, Annika JenmalmKarolinska Institutet (author)
  • Uhrbom, LeneUppsala universitet,Neuroonkologi,Science for Life Laboratory, SciLifeLab(Swepub:uu)leneuhrb (author)
  • Altelaar, A. F. MaartenKarolinska Institutet (author)
  • Linnarsson, StenKarolinska Institutet (author)
  • Uhlen, PerKarolinska Institutet (author)
  • Trantirek, Lukas (author)
  • Vincent, C. Theresa (author)
  • Nelander, SvenUppsala universitet,Neuroonkologi,Science for Life Laboratory, SciLifeLab(Swepub:uu)svene843 (author)
  • Enger, Per Oyvind (author)
  • Andang, Michael (author)
  • Uppsala universitetScience for Life Laboratory, SciLifeLab (creator_code:org_t)

Related titles

  • In:Cancer Research: AMER ASSOC CANCER RESEARCH77:7, s. 1741-17520008-54721538-7445

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