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Cancers 2019, 11(4), 525; https://doi.org/10.3390/cancers11040525

Transient Receptor Potential Mucolipin-1 Channels in Glioblastoma: Role in Patient’s Survival

1
School of Pharmacy, University of Camerino, 62032 Camerino, Italy
2
School of Biosciences and Veterinary Medicine, University of Camerino, 62032 Camerino, Italy
3
IRCCS NEUROMED, 86077 Pozzilli, Italy
*
Author to whom correspondence should be addressed.
Received: 1 March 2019 / Accepted: 9 April 2019 / Published: 12 April 2019
(This article belongs to the Special Issue Ion Channels in Cancer)
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Abstract

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 [Ca2+]i 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. View Full-Text
Keywords: glioblastoma; TRP channel; TRPML-1; mucolipins; autophagy; overall survival glioblastoma; TRP channel; TRPML-1; mucolipins; autophagy; overall survival
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This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited (CC BY 4.0).

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Morelli, M.B.; Amantini, C.; Tomassoni, D.; Nabissi, M.; Arcella, A.; Santoni, G. Transient Receptor Potential Mucolipin-1 Channels in Glioblastoma: Role in Patient’s Survival. Cancers 2019, 11, 525.

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