Gene expressions of TRP channels in glioblastoma multiforme and relation with survival

Alptekin, Mehmet; Eroğlu, Secil; Tutar, Ediz; Sencan, Sevide; Geyik, Murat; Ulaşlı, Mustafa; Demiryürek, Abdullah Tuncay; Camcı, Celalettin

doi:10.1007/s13277-015-3577-x

Cited by 79 publications

(71 citation statements)

References 50 publications

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“…Changes in TRP channel expression were found in gliomas, and a significant relationship between overexpression of TRP genes and survival of patients has been recently reported [23–25]. …”

Section: Discussionmentioning

confidence: 99%

Overexpression of transient receptor potential mucolipin-2 ion channels in gliomas: role in tumor growth and progression

et al. 2016

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The Transient Receptor Potential (TRP) superfamily consists of cation-selective and non-selective ion channels playing an important role both in sensory physiology and in physiopathology in several complex diseases including cancers. Among TRP family, the mucolipin (TRPML1, −2, and −3) channels represent a distinct subfamily of endosome/lysosome Ca2+ channel proteins. Loss-of-function mutations in human TRPML-1 gene cause a neurodegenerative disease, Mucolipidosis Type IV, whereas at present no pathology has been associated to human TRPML-2 channels.Herein we found that human TRPML-2 is expressed both in normal astrocytes and neural stem/progenitor cells. By quantitative RT-PCR, western blot, cytofluorimetric and immunohistochemistry analysis we also demonstrated that TRPML-2 mRNA and protein are expressed at different levels in glioma tissues and high-grade glioma cell lines of astrocytic origin. TRPML-2 mRNA and protein levels increased with the pathological grade, starting from pylocitic astrocytoma (grade I) to glioblastoma (grade IV). Moreover, by RNA interference, we demonstrated a role played by TRPML-2 in survival and proliferation of glioma cell lines. In fact, knock-down of TRPML-2 inhibited the viability, altered the cell cycle, reduced the proliferation and induced apoptotic cell death in glioma cell lines. The DNA damage and apoptosis induced by TRPML-2 loss increased Ser139 H2AX phosphorylation and induced caspase-3 activation; furthermore, knock-down of TRPML-2 in T98 and U251 glioma cell lines completely abrogated Akt and Erk1/2 phosphorylation, as compared to untreated cells.Overall, the high TRPML-2 expression in glioma cells resulted in increased survival and proliferation signaling, suggesting a pro-tumorigenic role played by TRPML-2 in glioma progression.

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“…Changes in TRP channel expression were found in gliomas, and a significant relationship between overexpression of TRP genes and survival of patients has been recently reported [23–25]. …”

Section: Discussionmentioning

confidence: 99%

Overexpression of transient receptor potential mucolipin-2 ion channels in gliomas: role in tumor growth and progression

et al. 2016

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“…In the same view, TRPV1 mRNA was found to be over-expressed in GBM tissues as respect to NB and TRPV1 expression was significantly higher (5-fold) in GBM patients with higher OS (more than 12 months) as respect to that showing lower OS (less than 12 months) [25]. No data on the expression of TRPV1 variants in tumors have been provided so far.…”

Section: Discussionmentioning

confidence: 99%

“…Moreover, neural precursor cell stimulation of TRPV1 has been found to trigger high-grade glioma cell death, activating the ATF3 transcription factor controlling ER stress pathway [23, 24]. Finally, it has been recently reported at mRNA level, that TRPV1 was over-expressed in glioblastoma (GBM) patients with higher overall survival (OS, more than 12 months) as respect to those showing lower OS (less than 12 months) [25]. Since 5'UTRs of the human TRPV1 transcripts could play a role in TRPV1 stability and translational efficiency, we investigated the involvement of 5'UTR sequences in TRPV1 stability, regulation of TRPV1 protein synthesis and expression in GBM cell lines.…”

Section: Introductionmentioning

confidence: 99%

Post-transcriptional regulation of 5'-untranslated regions of human Transient Receptor Potential Vanilloid type-1 (TRPV-1) channels: role in the survival of glioma patients

et al. 2016

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The Transient Receptor Potential Vanilloid type-1 (TRPV1) channel is a nonselective cation channel belonging to the Transient Receptor Potential family; variation of its expression has been correlated to glioma progression. In human, TRPV1 transcripts display a remarkable homogeneity differing only for the 5'-untranslated region (5'UTR) sequence that generates four variants encoding the same protein. Herein, we investigated the role of the 5'UTR sequences in TRPV1 transcripts stability, regulation of translation, expression in glioma cells and tissues. In addition, the expression of 5'UTR TRPV1 variants as prognostic factor in the survival of glioblastoma patients was evaluated. The expression level for each 5'UTR and their stability was evaluated by RT-PCR analysis. The effect of rapamycin and interferon-gamma in 5'UTR-regulating TRPV1 translation was determined by western blot analysis in glioma cell lines. We demonstrated that the 5'UTR influences the stability and translation efficacy of TRPV1 transcripts, and that TRPV1 variant three (TRPV1 v3 ) was the most stable and the only variant expressed in GBM samples and in glioma stem-like cells. Furthermore, we found that TRPV1 v3 expression levels correlate with patient's survival, suggesting that it may represent a potential prognostic marker for patients with glioma.

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“…The TRPC1, TRPC6, TRPM2, TRPM3, TRPM7, TRPM8, TRPV1, and TRPV2 channels were significantly higher in GBM patients, and there was a positive association between TRP genes overexpression and the enhanced survival of these patients (Alptekin et al, 2015). Several recent studies have also suggested the potential of TRP channels as pharmacologic targets for cancer treatment.…”

Section: Calcium Channel-associated Transientmentioning

confidence: 93%

Calcium Channels and Associated Receptors in Malignant Brain Tumor Therapy

Morrone¹,

Gehring²,

Nicoletti³

2016

Mol Pharmacol

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Malignant brain tumors are highly lethal and aggressive. Despite recent advances in the current therapies, which include the combination of surgery and radio/chemotherapy, the average survival rate remains poor. Altered regulation of ion channels is part of the neoplastic transformation, which suggests that ion channels are involved in cancer. Distinct classes of calciumpermeable channels are abnormally expressed in cancer and are likely involved in the alterations underlying malignant growth. Specifically, cytosolic Ca 21 activity plays an important role in the regulation of cell proliferation, and Ca 21 signaling is altered in proliferating tumor cells. A series of previous studies emphasized the importance of the T-type low-voltage-gated calcium channels (VGCC) in different cancer types, including gliomas, and remarkably, pharmacologic inhibition of T-type VGCC caused antiproliferative effects and triggered apoptosis of human glioma cells. Other calcium permeable channels, such as transient receptor potential (TRP) channels, contribute to changes in Ca 21 by modulating the driving force for Ca 21 entry, and some TRP channels are required for proliferation and migration in gliomas. Furthermore, recent evidence shows that TRP channels contribute to the progression and survival of the glioblastoma patients. Likewise, the purinergic P2X7 receptor acts as a direct conduit for Ca 21 -influx and an indirect activator of voltage-gated Ca 21 -channel. Evidence also shows that P2X7 receptor activation is linked to elevated expression of inflammation promoting factors, tumor cell migration, an increase in intracellular mobilization of Ca 21 , and membrane depolarization in gliomas. Therefore, this review summarizes the recent findings on calcium channels and associated receptors as potential targets to treat malignant gliomas.

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Gene expressions of TRP channels in glioblastoma multiforme and relation with survival

Cited by 79 publications

References 50 publications

Overexpression of transient receptor potential mucolipin-2 ion channels in gliomas: role in tumor growth and progression

Overexpression of transient receptor potential mucolipin-2 ion channels in gliomas: role in tumor growth and progression

Post-transcriptional regulation of 5'-untranslated regions of human Transient Receptor Potential Vanilloid type-1 (TRPV-1) channels: role in the survival of glioma patients

Calcium Channels and Associated Receptors in Malignant Brain Tumor Therapy

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