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TRPM8 is required for survival and radioresistance of glioblastoma cells

Klumpp, D.; Frank, S. C. 1,2; Klumpp, L.; Sezgin, E. C.; Eckert, M.; Edalat, L.; Bastmeyer, M. 1,2; Zips, D.; Ruth, P.; Huber, S. M.
1 Zoologisches Institut (ZOO), Karlsruher Institut für Technologie (KIT)
2 Institut für Funktionelle Grenzflächen (IFG), Karlsruher Institut für Technologie (KIT)

Abstract:
TRPM8 is a Ca$^{2+}$-permeable nonselective cation channel belonging to the melastatin sub-group of the transient receptor potential (TRP) family. TRPM8 is aberrantly overexpressed in a variety of tumor entities including glioblastoma multiforme where it reportedly contributes to tumor invasion. The present study aimed to disclose further functions of TRPM8 in glioma biology in particular upon cell injury by ionizing radiation. To this end, TCGA data base was queried to expose the TRPM8 mRNA abundance in human glioblastoma specimens and immunoblotting was performed to analyze the TRPM8 protein abundance in primary cultures of human glioblastoma. Moreover, human glioblastoma cell lines were irradiated with 6 MV photons and TRPM8 channels were targeted pharmacologically or by RNA interference. TRPM8 abundance, Ca$^{2+}$ signaling and resulting K$^{+}$ channel activity, chemotaxis, cell migration, clonogenic survival, DNA repair, apoptotic cell death, and cell cycle control were determined by qRT-PCR, fura-2 Ca$^{2+}$ imaging, patch-clamp recording, transfilter migration assay, wound healing assay, colony formation assay, immunohistology, flow cytometry, and immunoblotting. ... mehr


Verlagsausgabe §
DOI: 10.5445/IR/1000076724
Veröffentlicht am 04.04.2018
Originalveröffentlichung
DOI: 10.18632/oncotarget.21436
Scopus
Zitationen: 27
Web of Science
Zitationen: 25
Dimensions
Zitationen: 31
Cover der Publikation
Zugehörige Institution(en) am KIT Institut für Funktionelle Grenzflächen (IFG)
Zoologisches Institut (ZOO)
Publikationstyp Zeitschriftenaufsatz
Publikationsjahr 2017
Sprache Englisch
Identifikator ISSN: 1949-2553
urn:nbn:de:swb:90-767245
KITopen-ID: 1000076724
HGF-Programm 47.02.06 (POF III, LK 01) Zellpopul.auf Biofunk.Oberflächen IFG
Erschienen in OncoTarget
Verlag Impact Journals
Band 8
Heft 56
Seiten 95896-95913
Vorab online veröffentlicht am 30.09.2017
Schlagwörter glioblastoma; radioresistance; TRPM8 channels; Ca$^{2+}$ signaling; cell migration
Nachgewiesen in Web of Science
Dimensions
Scopus
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