The role of G protein-coupled receptors in lymphoid malignancies

Nugent, Adrienne; Proia, Richard L.

doi:10.1016/j.cellsig.2017.08.002

Cited by 22 publications

(16 citation statements)

References 205 publications

(330 reference statements)

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“…JBC REVIEWS: Illuminating the Onco-GPCRome been shown to have significant association with glioblastoma (GBM) (85) and lymphoblastic leukemia (86), and the evaluation of the impact of GPR98 mutations in cancer warrants further investigation. The family of metabotropic glutamate GPCRs, GRM1-8, are also frequently mutated in many cancer cohorts.…”

Section: Mutated Oncogpcromementioning

confidence: 99%

Illuminating the Onco-GPCRome: Novel G protein–coupled receptor-driven oncocrine networks and targets for cancer immunotherapy

Wu¹,

Yeerna²,

Nohata³

et al. 2019

Journal of Biological Chemistry

149

140

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Edited by Henrik G. Dohlman G protein-coupled receptors (GPCRs) are the largest gene family of cell membrane-associated molecules mediating signal transmission, and their involvement in key physiological functions is well-established. The ability of GPCRs to regulate a vast array of fundamental biological processes, such as cardiovascular functions, immune responses, hormone and enzyme release from endocrine and exocrine glands, neurotransmission, and sensory perception (e.g. vision, odor, and taste), is largely due to the diversity of these receptors and the layers of their downstream signaling circuits. Dysregulated expression and aberrant functions of GPCRs have been linked to some of the most prevalent human diseases, which renders GPCRs one of the top targets for pharmaceutical drug development. However, the study of the role of GPCRs in tumor biology has only just begun to make headway. Recent studies have shown that GPCRs can contribute to the many facets of tumorigenesis, including proliferation, survival, angiogenesis, invasion, metastasis, therapy resistance, and immune evasion. Indeed, GPCRs are widely dysregulated in cancer and yet are underexploited in oncology. We present here a comprehensive analysis of GPCR gene expression, copy number variation, and mutational signatures in 33 cancer types. We also highlight the emerging role of GPCRs as part of oncocrine networks promoting tumor growth, dissemination, and immune evasion, and we stress the potential benefits of targeting GPCRs and their signaling circuits in the new era of precision medicine and cancer immunotherapies. The G protein-coupled receptor (GPCR) 7 family of proteins includes over 800 members and comprises ϳ4% of the encoded human genome, making it the largest gene family involved in signal transduction (1, 2). Common to all GPCRs is the 7-transmembrane domain structure, which has an extracellular N terminus and an intracellular C terminus. The importance of the multiple biological roles GPCRs is reflected in the range of key physiological processes that they regulate, including vision, olfaction, neurotransmission, hormone and enzyme release, immune response, hemostasis, cardiac response and blood pressure regulation, epithelial cell renewal, stem cell fate decisions, tissue development, and homeostasis. In fact, dysfunction of GPCRs contributes to some of the most prevalent

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Section: Mutated Oncogpcromementioning

confidence: 99%

Illuminating the Onco-GPCRome: Novel G protein–coupled receptor-driven oncocrine networks and targets for cancer immunotherapy

Wu¹,

Yeerna²,

Nohata³

et al. 2019

Journal of Biological Chemistry

149

140

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“…Regarding the effects of GPR30 on B lymphocytes, some reports have mentioned that different chemokines can activate it, triggering different roles of B subsets such as migration, chemotaxis, proliferation, and apoptosis, among others. In fact, this receptor has been correlated with different B cell malignancies such as leukemia and lymphomas (135, 136). Nevertheless, more information or mechanisms of action related to this topic would be interesting in relation to the pathogenesis of breast cancer.…”

Section: Estrogen Effects On Immune System Cellsmentioning

confidence: 99%

Immune Tumor Microenvironment in Breast Cancer and the Participation of Estrogen and Its Receptors in Cancer Physiopathology

2019

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Breast cancer is characterized by cellular and molecular heterogeneity. Several molecular events are involved in controlling malignant cell processes. In this sense, there is an overriding importance to study the multiple cell alterations within this pathology. That the immune response can vary depending on sex is a widely identified fact. Steroid hormones and their receptors may regulate different functions and the responses of several subpopulations of the immune system. Few reports are focused on the function of estrogen receptors (ERs) on immune cells and their roles in different breast cancer subtypes. Thus, the aim of this review is to investigate the immune infiltrating tumor microenvironment and the prognosis conferred by it in different breast cancer subtypes, to discuss the current knowledge and to point out the roles of estrogen and its receptors on the infiltrating immune cells, as well as to identify how different immune subsets are modulated after anti-hormonal treatments in breast cancer patients.

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“…GPCRomics can help identify a role for individual and groups of GPCRs in health and disease and reveal "new" GPCRs as drug targets, thus providing a basis for drug discovery efforts or repurposing of approved drugs. It may identify previously unrecognized GPCRs in diseases, including in types of cancer that are major contributors to morbidity and mortality but for which GPCRs have been largely ignored as targets (e.g., [18,23,25,32,[69][70][71][72][73][74][75]). However, numerous questions exist in the field (see Outstanding Questions) and will likely be addressed in future studies.…”

Section: Discussionmentioning

confidence: 99%

GPCRomics: An Approach to Discover GPCR Drug Targets

Insel

Sriram

Gorr

et al. 2019

Trends in Pharmacological Sciences

145

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G protein-coupled receptors (GPCRs) are targets for ~35% of approved drugs but only ~15% of the ~800 human GPCRs are currently such targets. GPCRomics, the use of unbiased, hypothesisgenerating methods (e.g., RNA-sequencing [RNA-seq]), with tissues and cell types to identify and quantify GPCR expression, has led to the discovery of previously unrecognized GPCRs that contribute to functional responses and pathophysiology and that may be therapeutic targets. The combination of GPCR expression data with validation studies (e.g., signaling and functional activities) provides opportunities for the discovery of disease-relevant GPCR targets and therapeutics. Here, we review insights from GPCRomic approaches, gaps in knowledge and future directions by which GPCRomics can advance GPCR biology and the discovery of new GPCRtargeted drugs.

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The role of G protein-coupled receptors in lymphoid malignancies

Cited by 22 publications

References 205 publications

Illuminating the Onco-GPCRome: Novel G protein–coupled receptor-driven oncocrine networks and targets for cancer immunotherapy

Illuminating the Onco-GPCRome: Novel G protein–coupled receptor-driven oncocrine networks and targets for cancer immunotherapy

Immune Tumor Microenvironment in Breast Cancer and the Participation of Estrogen and Its Receptors in Cancer Physiopathology

GPCRomics: An Approach to Discover GPCR Drug Targets

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