Glioblastoma multiforme is the most aggressive tumor in central nervous system. It is characterized by the presence of an undifferentiated cell population named Glioblastoma Cancer Stem Cells (GSCs). Some embryonic genes can be reactivated in GSCs during malignant transformation, such as muscarinic receptors. Many reports suggest that muscarinic receptors can be involved in the regulation of the cell cycle, chemotaxis, and angiogenesis both in normal and in tumor tissues. Recently we demonstrated that M2 receptor activation by orthosteric and allosteric agonists, inhibited cell proliferation1,2 and counteracted cell survival involving PIP3K/AKT/mTOR pathway. β-Arrestins are ubiquitously proteins coupled with GPCR. The best-known is β1-arrestin. It can regulate the GPCR desensitization and participate in the modulation of signal transduction pathways, cytoskeleton remodeling, cell proliferation, migration, and in the controlling of gene expression3. In this context, we started to investigate the possible interaction between β1-arrestin and M2 mAChR in GSCs and the possible modulation of β1-arrestin modulation after M2 receptor activation. The first data obtained demonstrate that the M2 stimulation caused a downregulation of B1-arrestin and its progressive translocation from nuclei to the cytoplasm. The interaction between M2 receptor and β1-arrestin was evaluated in transfected GBM cell lines and GSCs, with two constructs overexpressing the two proteins conjugated with Flag and GFP respectively4 and by GST pull down. The first data obtained may contribute to better understanding the possible mechanisms downstream M2 muscarinic receptors and the role of β1-arrestin in this context.
“Interaction between β-Arrestin1 and M2 muscarinic receptors in Glioblastoma Cancer Stem Cells: implication in cell proliferation and survival” / Guerriero, Claudia; Scanavino1, Giulia; Masi, Ilenia; Lupo, Giuseppe; Matejcek, Marzia; Rosanò, Laura; Tata, Ada Maria. - In: EUROPEAN JOURNAL OF HISTOCHEMISTRY. - ISSN 2038-8306. - 67:s3(2023), pp. 21-22. (Intervento presentato al convegno Congress of the Italian Embryological Group-Italian Society of Development and Cell Biology (GEI-SIBSC) tenutosi a Oliveri (ME)) [10.4081/ejh.2023.3836].
“Interaction between β-Arrestin1 and M2 muscarinic receptors in Glioblastoma Cancer Stem Cells: implication in cell proliferation and survival”
Ilenia Masi;Ada Maria Tata
2023
Abstract
Glioblastoma multiforme is the most aggressive tumor in central nervous system. It is characterized by the presence of an undifferentiated cell population named Glioblastoma Cancer Stem Cells (GSCs). Some embryonic genes can be reactivated in GSCs during malignant transformation, such as muscarinic receptors. Many reports suggest that muscarinic receptors can be involved in the regulation of the cell cycle, chemotaxis, and angiogenesis both in normal and in tumor tissues. Recently we demonstrated that M2 receptor activation by orthosteric and allosteric agonists, inhibited cell proliferation1,2 and counteracted cell survival involving PIP3K/AKT/mTOR pathway. β-Arrestins are ubiquitously proteins coupled with GPCR. The best-known is β1-arrestin. It can regulate the GPCR desensitization and participate in the modulation of signal transduction pathways, cytoskeleton remodeling, cell proliferation, migration, and in the controlling of gene expression3. In this context, we started to investigate the possible interaction between β1-arrestin and M2 mAChR in GSCs and the possible modulation of β1-arrestin modulation after M2 receptor activation. The first data obtained demonstrate that the M2 stimulation caused a downregulation of B1-arrestin and its progressive translocation from nuclei to the cytoplasm. The interaction between M2 receptor and β1-arrestin was evaluated in transfected GBM cell lines and GSCs, with two constructs overexpressing the two proteins conjugated with Flag and GFP respectively4 and by GST pull down. The first data obtained may contribute to better understanding the possible mechanisms downstream M2 muscarinic receptors and the role of β1-arrestin in this context.I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.