Transient Receptor Potential Mucolipin-1 Channels in Glioblastoma: Role in Patient’s Survival
A link between mucolipin channels and tumors has been recently suggested. Herein, we aim to investigate the transient receptor potential mucolipin (TRPML)-1 relevance in glioblastoma. The expression of this channel was evaluated via qRT-PCR and immunohistochemistry in biopsies from 66 glioblastoma p...
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MDPI AG
2019-04-01
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| Series: | Cancers |
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| Online Access: | https://www.mdpi.com/2072-6694/11/4/525 |
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| author | Maria Beatrice Morelli Consuelo Amantini Daniele Tomassoni Massimo Nabissi Antonella Arcella Giorgio Santoni |
| author_facet | Maria Beatrice Morelli Consuelo Amantini Daniele Tomassoni Massimo Nabissi Antonella Arcella Giorgio Santoni |
| author_sort | Maria Beatrice Morelli |
| collection | DOAJ |
| description | A link between mucolipin channels and tumors has been recently suggested. Herein, we aim to investigate the transient receptor potential mucolipin (TRPML)-1 relevance in glioblastoma. The expression of this channel was evaluated via qRT-PCR and immunohistochemistry in biopsies from 66 glioblastoma patients and two human glioblastoma cell lines and compared to normal human brain, astrocytes, and epileptic tissues. The subcellular distribution of TRPML-1 was examined via confocal microscopy in the glioma cell lines. Then, to assess the role of TRPML-1, cell viability assays have been conducted in T98 and U251 cell lines treated with the specific TRPML-1 agonist, MK6-83. We found that MK6-83 reduced cell viability and induced caspase-3-dependent apoptosis. Indeed, the TRPML-1 silencing or the blockage of TRPML-1 dependent [Ca<sup>2+</sup>]<sub>i</sub> release abrogated these effects. In addition, exposure of glioma cells to the reactive oxygen species (ROS) inducer, carbonyl cyanide m-chlorophenylhydrazone (CCCP), stimulated a TRPML-1-dependent autophagic cell death, as demonstrated by the ability of the autophagic inhibitor bafilomycin A, the TRPML-1 inhibitor sphingomyelin, and the TRPML-1 silencing to completely inhibit the CCCP-mediated effects. To test a possible correlation with patient’s survival, Kaplan–Meier, univariate, and multivariate analysis have been performed. Data showed that the loss/reduction of TRPML-1 mRNA expression strongly correlates with short survival in glioblastoma (GBM) patients, suggesting that the reduction of TRPML-1 expression represents a negative prognostic factor in GBM patients. |
| first_indexed | 2024-03-12T19:59:47Z |
| format | Article |
| id | doaj.art-55e61a1978ab45b0b62b26eca328f095 |
| institution | Directory Open Access Journal |
| issn | 2072-6694 |
| language | English |
| last_indexed | 2024-03-12T19:59:47Z |
| publishDate | 2019-04-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Cancers |
| spelling | doaj.art-55e61a1978ab45b0b62b26eca328f0952023-08-02T02:30:45ZengMDPI AGCancers2072-66942019-04-0111452510.3390/cancers11040525cancers11040525Transient Receptor Potential Mucolipin-1 Channels in Glioblastoma: Role in Patient’s SurvivalMaria Beatrice Morelli0Consuelo Amantini1Daniele Tomassoni2Massimo Nabissi3Antonella Arcella4Giorgio Santoni5School of Pharmacy, University of Camerino, 62032 Camerino, ItalySchool of Biosciences and Veterinary Medicine, University of Camerino, 62032 Camerino, ItalySchool of Biosciences and Veterinary Medicine, University of Camerino, 62032 Camerino, ItalySchool of Pharmacy, University of Camerino, 62032 Camerino, ItalyIRCCS NEUROMED, 86077 Pozzilli, ItalySchool of Pharmacy, University of Camerino, 62032 Camerino, ItalyA link between mucolipin channels and tumors has been recently suggested. Herein, we aim to investigate the transient receptor potential mucolipin (TRPML)-1 relevance in glioblastoma. The expression of this channel was evaluated via qRT-PCR and immunohistochemistry in biopsies from 66 glioblastoma patients and two human glioblastoma cell lines and compared to normal human brain, astrocytes, and epileptic tissues. The subcellular distribution of TRPML-1 was examined via confocal microscopy in the glioma cell lines. Then, to assess the role of TRPML-1, cell viability assays have been conducted in T98 and U251 cell lines treated with the specific TRPML-1 agonist, MK6-83. We found that MK6-83 reduced cell viability and induced caspase-3-dependent apoptosis. Indeed, the TRPML-1 silencing or the blockage of TRPML-1 dependent [Ca<sup>2+</sup>]<sub>i</sub> release abrogated these effects. In addition, exposure of glioma cells to the reactive oxygen species (ROS) inducer, carbonyl cyanide m-chlorophenylhydrazone (CCCP), stimulated a TRPML-1-dependent autophagic cell death, as demonstrated by the ability of the autophagic inhibitor bafilomycin A, the TRPML-1 inhibitor sphingomyelin, and the TRPML-1 silencing to completely inhibit the CCCP-mediated effects. To test a possible correlation with patient’s survival, Kaplan–Meier, univariate, and multivariate analysis have been performed. Data showed that the loss/reduction of TRPML-1 mRNA expression strongly correlates with short survival in glioblastoma (GBM) patients, suggesting that the reduction of TRPML-1 expression represents a negative prognostic factor in GBM patients.https://www.mdpi.com/2072-6694/11/4/525glioblastomaTRP channelTRPML-1mucolipinsautophagyoverall survival |
| spellingShingle | Maria Beatrice Morelli Consuelo Amantini Daniele Tomassoni Massimo Nabissi Antonella Arcella Giorgio Santoni Transient Receptor Potential Mucolipin-1 Channels in Glioblastoma: Role in Patient’s Survival Cancers glioblastoma TRP channel TRPML-1 mucolipins autophagy overall survival |
| title | Transient Receptor Potential Mucolipin-1 Channels in Glioblastoma: Role in Patient’s Survival |
| title_full | Transient Receptor Potential Mucolipin-1 Channels in Glioblastoma: Role in Patient’s Survival |
| title_fullStr | Transient Receptor Potential Mucolipin-1 Channels in Glioblastoma: Role in Patient’s Survival |
| title_full_unstemmed | Transient Receptor Potential Mucolipin-1 Channels in Glioblastoma: Role in Patient’s Survival |
| title_short | Transient Receptor Potential Mucolipin-1 Channels in Glioblastoma: Role in Patient’s Survival |
| title_sort | transient receptor potential mucolipin 1 channels in glioblastoma role in patient s survival |
| topic | glioblastoma TRP channel TRPML-1 mucolipins autophagy overall survival |
| url | https://www.mdpi.com/2072-6694/11/4/525 |
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