Abstract:
:Despite decades of research, primary brain tumors, gliomas, lack effective treatment options and present a huge clinical challenge. Particularly, the most malignant subtype, Glioblastoma multiforme, proliferates extensively and cells often undergo incomplete cell divisions, resulting in multinucleated cells. We now present evidence that multinucleated glioma cells result from the functional loss of transient receptor potential canonical 1 (TRPC1) channels, plasma membrane proteins involved in agonist-induced calcium entry and reloading of intracellular Ca(2+) stores. Pharmacological inhibition or shRNA mediated suppression of TRPC1 causes loss of functional channels and store-operated calcium entry in D54MG glioma cells. This is associated with reduced cell proliferation and, frequently, with incomplete cell division. The resulting multinucleated cells are reminiscent of those found in patient biopsies. In a flank tumor model, tumor size was significantly decreased when TRPC1 expression was disrupted using a doxycycline inducible shRNA knockdown approach. These results suggest that TRPC1 channels play an important role in glioma cell division most likely by regulating calcium signaling during cytokinesis.
journal_name
Gliajournal_title
Gliaauthors
Bomben VC,Sontheimer Hdoi
10.1002/glia.20994subject
Has Abstractpub_date
2010-08-01 00:00:00pages
1145-56issue
10eissn
0894-1491issn
1098-1136journal_volume
58pub_type
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