2010
DOI: 10.1158/0008-5472.can-09-2654
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Receptor Channel TRPC6 Is a Key Mediator of Notch-Driven Glioblastoma Growth and Invasiveness

Abstract: Glioblastoma multiforme (GBM) is the most frequent and incurable type of brain tumor of adults. Hypoxia has been shown to direct GBM toward a more aggressive and malignant state. Here we show that hypoxia increases Notch1 activation, which in turn induces the expression of transient receptor potential 6 (TRPC6) in primary samples and cell lines derived from GBM. TRPC6 is required for the development of the aggressive phenotype because knockdown of TRPC6 expression inhibits glioma growth, invasion, and angiogen… Show more

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Cited by 182 publications
(168 citation statements)
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References 49 publications
(69 reference statements)
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“…Hypoxia treatment (CoCl 2 treatment) could activate TRPC6 channels and boost the ability of glioma proliferation and invasion. Inhibition of TRPC6 channels reversed the hypoxia-induced proliferation and invasion (Chigurupati et al, 2010). It is known that Notch signaling pathway is important for development and for maintaining cells in an undifferentiated state by regulating the transcription of many critical proteins (Artavanis-Tsakonas et al, 1999), these results suggest that Notch-induced TRPC6 expression may enhance undifferentiated state of glioma cells and therefore enhance the aggressiveness of glioma cells.…”
Section: Implication Of Trpc Channels In Glioma Progression and Therapymentioning
confidence: 73%
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“…Hypoxia treatment (CoCl 2 treatment) could activate TRPC6 channels and boost the ability of glioma proliferation and invasion. Inhibition of TRPC6 channels reversed the hypoxia-induced proliferation and invasion (Chigurupati et al, 2010). It is known that Notch signaling pathway is important for development and for maintaining cells in an undifferentiated state by regulating the transcription of many critical proteins (Artavanis-Tsakonas et al, 1999), these results suggest that Notch-induced TRPC6 expression may enhance undifferentiated state of glioma cells and therefore enhance the aggressiveness of glioma cells.…”
Section: Implication Of Trpc Channels In Glioma Progression and Therapymentioning
confidence: 73%
“…TRPC channels regulate neuronal survival, neurite development, synapse formation, axon guidance, endothelial permeability, cell migration, differentiation and proliferation (Ahmmed & Malik, 2005;Cai et al, 2006;Florio Pla et al, 2005;Jia et al, 2007;Li et al, 2005;Louis et al, 2008;Tai et al, 2008;Zhou et al, 2008;). Among the seven TRPC members, TRPC1 and TRPC6 have been reported to play important roles in glioma cell proliferation, migration and invasion, TRPC6 channels are also involved in tumor angiogenesis Chigurupati et al, 2010;Ding et al, 2010;Ge et al, 2009;Hamdollah Zadeh et al, 2008 Table 2. Schematic topology of subunit and subunit assembly of glioma-related ion channels.…”
Section: Implication Of Trpc Channels In Glioma Progression and Therapymentioning
confidence: 99%
“…In this context, the recent interest in human 'transportome' involvement in tumour vascularization is a promising field, because several members are activated downstream of the recruitment of VEGF receptors. For example, whereas the interference with the bulk VEGF signalling alters the activity of a multitude of different cells and functions, targeting TRPC6 or Orai1 may affect only EC migration and proliferation [31,34,44,53,92], whereas TRPC1 and STIM1 may selectively influence vascular permeability [56][57][58]61].…”
Section: Resultsmentioning
confidence: 99%
“…For example, TRPC6 channels targeting could affect VEGF release from tumour cells as well as EC migration and tumour vascularization [31,44,53].…”
Section: Resultsmentioning
confidence: 99%
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