Metabotyping human endometrioid endometrial adenocarcinoma reveals an implication of endocannabinoid metabolism

Jové, Mariona; Gatius, Sònia; Yeramian, Andrée; Portero‐Otín, Manuel; Eritja, Núria; Santacana, Maria; Colás, Eva; Ruiz, Manuel; Pamplona, Reinald; Matías‐Guiu, Xavier

doi:10.18632/oncotarget.10564

Cited by 21 publications

(27 citation statements)

References 33 publications

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“…We also observed a downregulation of the acylamido analogs of endocannabinoids such as palmitamide, stearamide and oleamide in EC. This downregulation has been previously reported 33 . We also observed a decreased proportion of picolinic acid in tumor samples.…”

Section: Discussionsupporting

confidence: 87%

Metabolomic and Lipidomic Profiling Identifies The Role of the RNA Editing Pathway in Endometrial Carcinogenesis

Altadill

Dowdy

Gill

et al. 2017

Sci Rep

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Endometrial cancer (EC) remains the most common malignancy of the genital tract among women in developed countries. Although much research has been performed at genomic, transcriptomic and proteomic level, there is still a significant gap in the metabolomic studies of EC. In order to gain insights into altered metabolic pathways in the onset and progression of EC carcinogenesis, we used high resolution mass spectrometry to characterize the metabolomic and lipidomic profile of 39 human EC and 17 healthy endometrial tissue samples. Several pathways including lipids, Kynurenine pathway, endocannabinoids signaling pathway and the RNA editing pathway were found to be dysregulated in EC. The dysregulation of the RNA editing pathway was further investigated in an independent set of 183 human EC tissues and matched controls, using orthogonal approaches. We found that ADAR2 is overexpressed in EC and that the increase in expression positively correlates with the aggressiveness of the tumor. Furthermore, silencing of ADAR2 in three EC cell lines resulted in a decreased proliferation rate, increased apoptosis, and reduced migration capabilities in vitro. Taken together, our results suggest that ADAR2 functions as an oncogene in endometrial carcinogenesis and could be a potential target for improving EC treatment strategies.

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Section: Discussionsupporting

confidence: 87%

Metabolomic and Lipidomic Profiling Identifies The Role of the RNA Editing Pathway in Endometrial Carcinogenesis

Altadill

Dowdy

Gill

et al. 2017

Sci Rep

Self Cite

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“…Furthermore, metabolomics studies demonstrated that there are differences in cellular metabolism between myometrial invasion front and non-invasive endometrial cancer cells. In fact, about invasive front there is an increased expression of endocannabinoid-like metabolites like stearamide and this confirm the potential involvement of ECS in tumoral invasion [65]. A recent study showed that the ECS maybe act as antagonist of the estrogen and in general, it could contrast increasing level of sex hormones playing a protective role in the development of hormones related cancers [66].…”

Section: The Endocannabinoid System Ad Endometrial Cancermentioning

confidence: 70%

The Role of the Endocannabinoid System in the Gynaecological Malignancy

Grauso¹,

Autiero²,

Gr³

et al. 2018

Preprint

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Background: The endocannabinoid system (ECS) is a very heterogeneous array consisting of many proteins like ligands, enzymes and receptors synthetized in various tissues and immunity cells. The main endogenous ligands are unsaturated fatty acid derivatives like anandamide(AEA), 2-arachidonoylglycerol(2-AG), but many others are under study. Endocannabinoids are involved in both physiological and pathological conditions. ECS plays an important role in the regulation of main processes which lead to cancer and also in sex steroid hormone-related cancers.Methods: With focus on gynaecological cancers, main papers and review articles, up to April 2018, on the role of the ECS, were acquired by PubMed searches using the search terms: ‘cancer’, ‘cannabinoid’, ‘endocannabinoid’, ‘gynaecology’ and ‘malignancy’.Results: The review of recent literature data showed the involvement of the endocannabinoid system in numerous physiological and pathological conditions of the female genital tract up to the development of gynaecological malignancy as cervical, endometrial and ovarian cancer.Conclusions: The endocannabinoid system has an important role in antitumor actions involving different signalling receptor and receptor-independent pathways. It represents an exciting challenge to researchers for its potential use in diagnosis and treatment of all gynaecological malignancies

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“…Furthermore, 2-AG levels were increased but MAGL expression was decreased in comparison to controls, while AEA levels and FAAH expression were unaffected [114]. In accordance with these findings, Jové et al [115] demonstrated that CB 2 was expressed at higher levels in stages III and IV of endometrial carcinoma, which has been linked to a poor prognosis. Contrary to Guida et al[114], they found an increase in CB 1 expression by immunohistochemistry in endometrial carcinoma tissue compared to normal endometrial tissue [115].…”

Section: The Ecs In Gynecological Disorders and Cancermentioning

confidence: 80%

Cannabinoids in Gynecological Diseases

Luschnig

Schicho

2019

Med Cannabis Cannabinoids

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The endocannabinoid system (ECS) is a multifunctional homeostatic system involved in many physiological and pathological conditions. The ligands of the ECS are the endocannabinoids, whose actions are mimicked by exogenous cannabinoids, such as phytocannabinoids and synthetic cannabinoids. Responses to the ligands of the ECS are mediated by numerous receptors like the classical cannabinoid receptors (CB1 and CB2) as well as ECS-related receptors, e.g., G protein-coupled receptors 18 and 55 (GPR18 and GPR55), transient receptor potential ion channels, and nuclear peroxisome proliferator-activated receptors. The ECS regulates almost all levels of female reproduction, starting with oocyte production through to parturition. Dysregulation of the ECS is associated with the development of gynecological disorders from fertility disorders to cancer. Cannabinoids that act at the ECS as specific agonists or antagonists may potentially influence dysregulation and, therefore, represent new therapeutic options for the therapy of gynecological disorders.

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Metabotyping human endometrioid endometrial adenocarcinoma reveals an implication of endocannabinoid metabolism

Cited by 21 publications

References 33 publications

Metabolomic and Lipidomic Profiling Identifies The Role of the RNA Editing Pathway in Endometrial Carcinogenesis

Metabolomic and Lipidomic Profiling Identifies The Role of the RNA Editing Pathway in Endometrial Carcinogenesis

The Role of the Endocannabinoid System in the Gynaecological Malignancy

Cannabinoids in Gynecological Diseases

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