ArticleBritish journal of pharmacology2011
The cannabinoid receptor inverse agonist AM251 regulates the expression of the EGF receptor and its ligands via destabilization of oestrogen-related receptor α protein.
Article in British journal of pharmacology, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.
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Who cites it
17 citing papers in PubMed, 24 citations in OpenAlex.
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- Cannabinoid Receptor-1 suppresses M2 macrophage polarization in colorectal cancer by downregulating EGFR.Cell death discovery · 2022Article
- The Endocannabinoid System: A Potential Target for the Treatment of Various Diseases.International journal of molecular sciences · 2021Review
- The Complex Interplay between Endocannabinoid System and the Estrogen System in Central Nervous System and Periphery.International journal of molecular sciences · 2021Review
- Overexpression of cannabinoid receptor 1 promotes renal cell carcinoma progression.Tumour biology : the journal of the International Society for Oncodevelopmental Biology and Medicine · 2016Article
- Selective GPR55 antagonism reduces chemoresistance in cancer cells.Pharmacological research · 2016Article
- Endocannabinoid system as a regulator of tumor cell malignancy - biological pathways and clinical significance.OncoTargets and therapy · 2016Review
- Estrogen-related receptor α is required for efficient human cytomegalovirus replication.Proceedings of the National Academy of Sciences of the United States of America · 2014Article
- The estrogen-related receptor α inverse agonist XCT 790 is a nanomolar mitochondrial uncoupler.Biochemistry · 2014Article
- The influence of monoacylglycerol lipase inhibition upon the expression of epidermal growth factor receptor in human PC-3 prostate cancer cells.BMC research notes · 2014Article
- Inhibitory signaling by CB1 receptors in smooth muscle mediated by GRK5/β-arrestin activation of ERK1/2 and Src kinase.American journal of physiology. Gastrointestinal and liver physiology · 2014Article
- (R,R')-4'-methoxy-1-naphthylfenoterol targets GPR55-mediated ligand internalization and impairs cancer cell motility.Biochemical pharmacology · 2014Article
- Novel drugs that target the estrogen-related receptor alpha: their therapeutic potential in breast cancer.Cancer management and research · 2014Review
- Article
- The biarylpyrazole compound AM251 alters mitochondrial physiology via proteolytic degradation of ERRα.Molecular pharmacology · 2013Article
Corrections and comments
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Authors and funding
6 authors at 2 institutions in 2 countries.
Funding
Abstract
background and purposeAM251 is an inverse agonist of the cannabinoid 1 receptor (CB(1)R) that can exert 'off-target' effects in vitro and in CB(1)R knock-out mice. AM251 is also potent at modulating tumour cell growth, suggesting that growth factor-mediated oncogenic signalling could be regulated by AM251. Since dysregulation of the EGF receptor has been associated with carcinogenesis, we examined AM251 regulation of EGF receptor (EGFR) expression and function. EXPERIMENTAL APPROACH: The various biological functions of AM251 were measured in CB(1)R-negative human cancer cells. Pharmacological and genetic approaches were used to validate the data. KEY
resultsThe mRNA levels for EGFR and its associated ligands, including HB-EGF, were induced several fold in PANC-1 and HCT116 cells in response to AM251. This event was associated with enhanced expression of EGFR on the cell surface with concomitant increase in EGF-induced cellular responses in AM251-treated cells. Exposure to XCT790, a synthetic inverse agonist of the orphan nuclear oestrogen-related receptor α (ERRα), also induced EGFR and HB-EGF expression to the same extent as AM251, whereas pretreatment with the ERRα-selective agonist, biochanin A, blunted AM251 actions. AM251 promoted the degradation of ERRα protein without loss of the corresponding mRNA. Knock-down of ERRα by siRNA-based approach led to constitutive induction of EGFR and HB-EGF levels, and eliminated the biological responses of AM251 and XCT790. Finally, AM251 displaced diethylstilbestrol prebound to the ligand-binding domain of ERRα. CONCLUSIONS AND IMPLICATIONS: AM251 up-regulates EGFR expression and signalling via a novel non-CB(1)R-mediated pathway involving destabilization of ERRα protein in selected cancer cell lines.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.