G Protein-Coupled Receptor Signaling in Stem Cells and Cancer

Lynch, Jodi; Wang, Jenny

doi:10.3390/ijms17050707

Cited by 55 publications

(44 citation statements)

References 155 publications

(195 reference statements)

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“…Several studies have demonstrated a central role for GPCRs such as GPR84, WNT, S1P, or CXCR4 in HSC maintenance (Doze and Perez, 2013;Lynch and Wang, 2016), and dysregulation of these pathways can have detrimental consequences, including malignant transformation. Because each GPCR is expected to stimulate multiple and highly interconnected cytoplasmic signaling pathways, largely through activation of AKT/MTOR, MAPKs, Hippo, or the Wnt/β-catenin signaling pathways, they can influence a wide array of biological responses (Laplante and Sabatini, 2012;Yu et al, 2012;O'Hayre et al, 2014).…”

Section: Discussionmentioning

confidence: 99%

CD97 is a critical regulator of acute myeloid leukemia stem cell function

Martin

Roy

Chakraborty

et al. 2019

Journal of Experimental Medicine

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Despite significant efforts to improve therapies for acute myeloid leukemia (AML), clinical outcomes remain poor. Understanding the mechanisms that regulate the development and maintenance of leukemic stem cells (LSCs) is important to reveal new therapeutic opportunities. We have identified CD97, a member of the adhesion class of G protein–coupled receptors (GPCRs), as a frequently up-regulated antigen on AML blasts that is a critical regulator of blast function. High levels of CD97 correlate with poor prognosis, and silencing of CD97 reduces disease aggressiveness in vivo. These phenotypes are due to CD97’s ability to promote proliferation, survival, and the maintenance of the undifferentiated state in leukemic blasts. Collectively, our data credential CD97 as a promising therapeutic target on LSCs in AML.

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Section: Discussionmentioning

confidence: 99%

CD97 is a critical regulator of acute myeloid leukemia stem cell function

Martin

Roy

Chakraborty

et al. 2019

Journal of Experimental Medicine

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“…GPCR are transmembrane receptors that become activated upon the binding of extracellular ligands, propagating signals to cells . Their functions in mediating cell signals are extensive and crucial.…”

Section: Short‐chain Fatty Acids (Scfa)mentioning

confidence: 99%

Role of gut microbial metabolites in nonalcoholic fatty liver disease

Zhao

Lai

Qiao

et al. 2019

J of Digest Diseases

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Nonalcoholic fatty liver disease (NAFLD) is a common, multifactorial liver disease that has emerged as a global challenge due to its increasing prevalence and lack of sustainable treatment options. Gut microbiota possess vital functions in fermenting dietary nutrients and synthesizing bioactive molecules. This function is of great importance in maintaining health because these microbial metabolites are essential in regulating energy metabolism, immune response, and other vital physiological processes. Altered gut flora can result in a change in gut microbial metabolites, affecting the onset and progression of multiple diseases. In this review we summarize the metabolites that may have beneficial or harmful effects on the development and progression of NAFLD. This will help us better understand the possible mechanisms underlying the pathogenesis of NAFLD and facilitate the identification of potential therapeutic approaches for NAFLD.

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“…GPCRs respond to a wide range of extracellular signals and regulate various cellular and physiological processes, including hormone regulation, vision, immune responses, neuronal communication, and behavior [2]. Overwhelming evidences have demonstrated that GPCRs and their downstream signaling targets play critical roles in cancer initiation and progression by regulating signal transduction and cellular processes (including cell proliferation, apoptosis, stress signals, immune escape, invasion, angiogenesis and metastasis, ion and nutrient transport and migration) [3,4]. It has also been demonstrated that diverse GPCRs were overexpressed in a variety of tumors [5].…”

Section: Introductionmentioning

confidence: 99%

An Integrated Pan-Cancer Analysis and Structure-Based Virtual Screening of GPR15

Wang

Xiong

et al. 2019

IJMS

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G protein-coupled receptor 15 (GPR15, also known as BOB) is an extensively studied orphan G protein-coupled receptors (GPCRs) involving human immunodeficiency virus (HIV) infection, colonic inflammation, and smoking-related diseases. Recently, GPR15 was deorphanized and its corresponding natural ligand demonstrated an ability to inhibit cancer cell growth. However, no study reported the potential role of GPR15 in a pan-cancer manner. Using large-scale publicly available data from the Cancer Genome Atlas (TCGA) and the Genotype-Tissue Expression (GTEx) databases, we found that GPR15 expression is significantly lower in colon adenocarcinoma (COAD) and rectal adenocarcinoma (READ) than in normal tissues. Among 33 cancer types, GPR15 expression was significantly positively correlated with the prognoses of COAD, neck squamous carcinoma (HNSC), and lung adenocarcinoma (LUAD) and significantly negatively correlated with stomach adenocarcinoma (STAD). This study also revealed that commonly upregulated gene sets in the high GPR15 expression group (stratified via median) of COAD, HNSC, LUAD, and STAD are enriched in immune systems, indicating that GPR15 might be considered as a potential target for cancer immunotherapy. Furthermore, we modelled the 3D structure of GPR15 and conducted structure-based virtual screening. The top eight hit compounds were screened and then subjected to molecular dynamics (MD) simulation for stability analysis. Our study provides novel insights into the role of GPR15 in a pan-cancer manner and discovered a potential hit compound for GPR15 antagonists.

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G Protein-Coupled Receptor Signaling in Stem Cells and Cancer

Cited by 55 publications

References 155 publications

CD97 is a critical regulator of acute myeloid leukemia stem cell function

CD97 is a critical regulator of acute myeloid leukemia stem cell function

Role of gut microbial metabolites in nonalcoholic fatty liver disease

An Integrated Pan-Cancer Analysis and Structure-Based Virtual Screening of GPR15

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