M2 muscarinic receptors inhibit cell proliferation in human glioblastoma cell lines

Ferretti, M.; Fabbiano, C.; Bari, María Di; Ponti, Donatella; Calogero, Antonella; Tata, Ada Maria

doi:10.1016/j.lfs.2012.04.033

Cited by 26 publications

(41 citation statements)

References 14 publications

(19 reference statements)

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“…It stimulates production of connective tissue growth factor in human buccal mucosal fibroblasts and induces HaCaT cell apoptosis (Deng et al, 2009;Li et al, 2014). ARE could inhibit cell cycle progression or mediate phospholipase C-dependent activation of protein kinases in glioma cells through its binding to muscarinic receptors (Tang et al, 2002;Ferretti et al, 2012Ferretti et al, , 2013. Reports showed that glioma cells possess M2 muscarinic receptors, activation by acetylcholine could stimulate small-conductance Ca 2þ -activated K þ (SK Ca ) channels in neocortical pyramidal neurons (Brombas et al, 2014;Ferretti et al, 2012Ferretti et al, , 2013.…”

Section: Introductionmentioning

confidence: 99%

“…ARE could inhibit cell cycle progression or mediate phospholipase C-dependent activation of protein kinases in glioma cells through its binding to muscarinic receptors (Tang et al, 2002;Ferretti et al, 2012Ferretti et al, , 2013. Reports showed that glioma cells possess M2 muscarinic receptors, activation by acetylcholine could stimulate small-conductance Ca 2þ -activated K þ (SK Ca ) channels in neocortical pyramidal neurons (Brombas et al, 2014;Ferretti et al, 2012Ferretti et al, , 2013. ARE has been shown to suppress ether-à-gogo-related K þ current and stimulate muscarinic-K þ channels or ATPsensitive K þ channels (Chen, 2005;Yoshizumi et al, 2008;Ling et al, 2012;Zhao et al, 2012).…”

Section: Introductionmentioning

confidence: 99%

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Arecoline inhibits intermediate-conductance calcium-activated potassium channels in human glioblastoma cell lines

Huang

Hsing

et al. 2015

European Journal of Pharmacology

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Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Arecoline inhibits intermediate-conductance calcium-activated potassium channels in human glioblastoma cell lines

Huang

Hsing

et al. 2015

European Journal of Pharmacology

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“…29,30 In particular, several reports have shown that M3 muscarinic receptor activation enhances tumor cell proliferation, migration and angiogenesis. 19,24,31 However 27,28 suggesting that M2 receptors might play a counteracting role in tumor cell proliferation.…”

Section: Discussionmentioning

confidence: 99%

“…27,28 We thus investigated whether the M2 receptors could also mediate similar effects in a cell line derived from urothelial carcinoma (T24) after treatment with the M2 agonist Arecaidine. The T24 cells express all 3 muscarinic receptors analysed, yielding the following rank order of expression: M1 M2> M3 ( Fig.…”

Section: M2 Receptor Expression Is Proportional To the Histological Gmentioning

confidence: 99%

“…19,[24][25][26] However, we have recently demonstrated that the M2 receptor subtype is able to inhibit cell growth and survival in human glioblastoma cells, highlighting a role for this receptor in the inhibition of cancer cell proliferation. 27,28 In this study we attempt to investigate the expression of M2 muscarinic receptors in bladder cancer samples and to explore their biological effects on urothelial cancer cells as we already demonstrated in glioblastoma cells. Our results show that the M2 receptors are related to the tumor grade and that their selective stimulation strongly inhibits both in vitro proliferation and migration of T24 and 5637 cancer cells.…”

Section: Introductionmentioning

confidence: 99%

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M2 muscarinic receptors inhibit cell proliferation and migration in urothelial bladder cancer cells

Palleschi¹,

Pastore²,

Salhi³

et al. 2017

European Urology Supplements

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Polycomb complex mediated epigenetic reprogramming alters TGF‐β signaling via a novel EZH2/miR‐490/TGIF2 axis thereby inducing migration and EMT potential in glioblastomas

Vinchure

Sharma

Tabasum

et al. 2019

Intl Journal of Cancer

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Recent advancement in understanding cancer etiology has highlighted epigenetic deregulation as an important phenomenon leading to poor prognosis in glioblastoma (GBM). Polycomb repressive complex 2 (PRC2) is one such important epigenetic modifier reportedly altered in GBM. However, its defined mechanism in tumorigenesis still remains elusive. In present study, we analyzed our in‐house ChIPseq data for H3k27me3 modified miRNAs and identified miR‐490‐3p to be the most common target in GBM with significantly downregulated expression in glioma patients in both TCGA and GBM patient cohort. Our functional analysis delineates for the first time, a central role of PRC2 catalytic unit EZH2 in directly regulating expression of this miRNA and its host gene CHRM2 in GBM. In accordance, cell line treatment with EZH2 siRNA and 5‐azacytidine also confirmed its coregulation by CpG and histone methylation based epigenetic mechanisms. Furthermore, induced overexpression of miR‐490‐3p in GBM cell lines significantly inhibited key hallmarks including cellular proliferation, colony formation and spheroid formation, as well as epithelial‐to‐mesenchymal transition (EMT), with downregulation of multiple EMT transcription factors and promigratory genes (MMP9, CCL5, PIK3R1, ICAM1, ADAM17 and NOTCH1). We also for the first time report TGFBR1 and TGIF2 as two direct downstream effector targets of miR‐490‐3p that are also deregulated in GBM. TGIF2, a novel target, was shown to promote migration and EMT that could partially be rescued by miR‐490‐3p overexpression. Overall, this stands as a first study that provides a direct link between epigenetic modulator EZH2 and oncogenic TGF‐β signaling involving novel miR‐490‐3p/TGIF2/TGFBR1 axis, that being targetable might be promising in developing new therapeutic intervention strategies for GBM.

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M2 muscarinic receptors inhibit cell proliferation in human glioblastoma cell lines

Cited by 26 publications

References 14 publications

Arecoline inhibits intermediate-conductance calcium-activated potassium channels in human glioblastoma cell lines

Arecoline inhibits intermediate-conductance calcium-activated potassium channels in human glioblastoma cell lines

M2 muscarinic receptors inhibit cell proliferation and migration in urothelial bladder cancer cells

Polycomb complex mediated epigenetic reprogramming alters TGF‐β signaling via a novel EZH2/miR‐490/TGIF2 axis thereby inducing migration and EMT potential in glioblastomas

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