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

Autor: Francesco Rossi, Antonietta Arcella, Claudio Cardinali, Angela Santoni, Maria Paola Mariani, Consuelo Amantini, Carlo Polidori, Matteo Santoni, Giorgio Santoni, Maria Antonietta Oliva, Maria Beatrice Morelli, Massimo Nabissi, Daniele Tomassoni
Jazyk: angličtina
Rok vydání: 2016
Předmět:
0301 basic medicine
Pathology
Carcinogenesis
Biopsy
Apoptosis
mucolipin-2
Histones
Transient receptor potential channel
0302 clinical medicine
Transient Receptor Potential Channels
Phosphorylation
RNA
Small Interfering
Mitogen-Activated Protein Kinase 1
Mitogen-Activated Protein Kinase 3
Brain Neoplasms
Caspase 3
Cell Cycle
Glioma
Cell cycle
Immunohistochemistry
Oncogene Protein v-akt
medicine.anatomical_structure
Oncology
030220 oncology & carcinogenesis
Disease Progression
RNA Interference
Research Paper
medicine.medical_specialty
Cell Survival
proliferation
Biology
Real-Time Polymerase Chain Reaction
03 medical and health sciences
Lysosome
Cell Line
Tumor
medicine
Humans
Progenitor cell
Protein kinase B
Cell Proliferation
TRP channels
Cell Membrane
medicine.disease
Molecular medicine
gliomas
030104 developmental biology
Cancer research
Neoplasm Grading
Zdroj: Oncotarget
Popis: // Maria Beatrice Morelli 1, 2 , Massimo Nabissi 1 , Consuelo Amantini 3 , Daniele Tomassoni 3 , Francesco Rossi 1 , Claudio Cardinali 1, 2 , Matteo Santoni 4 , Antonietta Arcella 5 , Maria Antonietta Oliva 5 , Angela Santoni 2, 5 , Carlo Polidori 1 , Maria Paola Mariani 6 , Giorgio Santoni 1 1 School of Pharmacy, University of Camerino, Camerino, Italy 2 Department of Molecular Medicine, Sapienza University, Rome, Italy 3 School of Biosciences and Veterinary Medicine, University of Camerino, Camerino, Italy 4 Department of Medical Oncology, Polytechnic University of Marche, Ancona, Italy 5 I.N.M. Neuromed, Pozzilli, Isernia, Italy 6 Anatomo-Pathology Operative Unit, AV3 Macerata, Italy Correspondence to: Giorgio Santoni, email: giorgio.santoni@unicam.it Keywords: TRP channels, mucolipin-2, gliomas, proliferation, apoptosis Received: March 09, 2016 Accepted: May 01, 2016 Published: May 27, 2016 ABSTRACT 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 Ca 2+ 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.
Databáze: OpenAIRE
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