GPR56/ADGRG1 Inhibits Mesenchymal Differentiation and Radioresistance in Glioblastoma

Fernández, Marta; Pedrosa, Leire; Paré, Laia; Pineda, Estela; Bejarano, Leire; Martínez, Josefina; Balasubramaniyan, Veerakumar; Ezhilarasan, Ravesanker; Kallarackal, Naveen; Kim, Sung-Hak; Wang, Jia; Audia, Alessandra; Conroy, Siobhan; Marin, Michael; Ribalta, Teresa; Pujol, Teresa; Herreros, Antoni; Tortosa, Avelina; Mira, Helena; Alonso, Marta M.; Gómez-Manzano, Candelaria; Graus, Francesc; Sulman, Erik P.; Piao, Xiangshu; Nakano, ﻿Ichiro; Prat, Aleix; Bhat, Krishna; Iglesia, Núria de la

doi:10.1016/j.celrep.2017.10.083

Cited by 58 publications

(72 citation statements)

References 69 publications

(118 reference statements)

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“…Epigenetic silencing or experimental knockdown of ADGRB1 leads to enhanced granule neuron precursors proliferation by reduction of p53 tumour suppressor levels in these cells . ADGRG1 appears to serve a similar antitumorigenic function in several cancer types including glioblastomas, explaining why reduced ADGRG1 expression is associated with poor prognosis . Also on haematologic malignancies, aGPCR have documented impact.…”

Section: Adhesion Gpcr As Drug Targetsmentioning

confidence: 99%

Adhesion G protein–coupled receptors—Candidate metabotropic mechanosensors and novel drug targets

Langenhan

2019

Basic Clin Pharma Tox

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While a wide range of G protein-coupled receptors (GPCR) have emerged as prime targets for pharmacological intervention long ago, a distinct group of GPCR has only recently been identified and become a research subject to fundamental and clinical scientists. Adhesion-type GPCR (aGPCR) are exceptional members of the GPCR superfamily in many aspects: structurally, they appear as chimeric surface molecules that possess signature domains of heptahelical (7TM) and adhesion proteins, many aGPCR are autoproteolytically processed, and several homologues have lately been shown to operate as mechanosensors. Bound together by the recent discovery of tethered agonism in aGPCR, these molecular and functional features have entered first models on how aGPCR are activated. Here, I briefly review recent discoveries pertaining to the role of aGPCR as metabotropic mechanosensors that control a large variety of processes in all major tissue types.

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Section: Adhesion Gpcr As Drug Targetsmentioning

confidence: 99%

Adhesion G protein–coupled receptors—Candidate metabotropic mechanosensors and novel drug targets

Langenhan

2019

Basic Clin Pharma Tox

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“…Figure 5C). Additionally, GSEA results demonstrated that CXCL1 was associated with multiple molecular pathways related to malignancy and therapy resistance, including epithelial-mesenchymal transition 29 and NF-κB signaling 30 (Figure 5D and E).To further confirm the results of bioinformatics analysis, qRT-PCR and Western blot assays were carried out. The results showed that CXCL1 overexpression significantly enhanced the overall expression of NF-κB/ p65, indicating that NF-κB signaling might be activated by CXCL1.…”

Section: Cxcl1 Induced Radioresistance In Gbm Via Regulation Of Nf-mentioning

confidence: 79%

“…Recent studies have clarified that GBMs are highly plastic and have a natural tendency to transition from one subtype to another . This transcriptional plasticity enables GBM to rapidly gain resistance to radiotherapy . Intrinsic therapy resistance has been caused by the process of mesenchymal transition, by which GBM cells acquired mesenchymal properties through loss of cell‐cell adhesion, acquisition of invasive, and migratory capability .…”

Section: Discussionmentioning

confidence: 99%

“…21,27 This transcriptional plasticity enables GBM to rapidly gain resistance to radiotherapy. 30 Intrinsic therapy resistance has been caused by the process of mesenchymal transition, by which GBM cells acquired mesenchymal properties through loss of cellcell adhesion, acquisition of invasive, and migratory capability. 46 It has been well studied that mesenchymal transition is responsible for oncology as well as invasion, metastasis, and therapy resistance of cancer cells.…”

Section: Discussionmentioning

confidence: 99%

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Elevation of CXCL1 indicates poor prognosis and radioresistance by inducing mesenchymal transition in glioblastoma

Wahafu

Zuo

et al. 2020

CNS Neurosci Ther

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Introduction Glioblastoma (GBM) is identified as a lethal malignant tumor derived from the nervous system. Despite the standard clinical strategy including maximum surgical resection, temozolomide (TMZ) chemotherapy, and radiotherapy, the median survival of GBM patients remains <15 months. Accumulating evidence indicates that rapid‐acquired radioresistance is one of the most common reasons for GBM recurrence. Therefore, developing novel therapeutic targets for radioresistant GBM could yield long‐term cures. Aims To investigate the functional role of CXCL1 in the acquired radioresistance and identify the molecular pathway correlated to CXCL1. Results In this study, we identified that CXCL1 is highly expressed in GBM and the elevation of CXCL1 is involved in radioresistance and poor prognosis in GBM patients. Additionally, silencing CXCL1 attenuated the proliferation and radioresistance of GBM cells. Furthermore, we demonstrated that CXCL1‐overexpression induced radioresistance through mesenchymal transition of GBM via the activation of nuclear factor‐kappa B (NF‐κB) signaling. Conclusion CXCL1 was highly enriched in GBM and positively correlated with poor prognosis in GBM patients. Additionally, elevated CXCL1 induced radioresistance in GBM through regulation of NF‐κB signaling by promoting mesenchymal transition in GBM.

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“…However, there were also studies showing that high expression of SOCS2 in paediatric AML patients had an inferior prognosis . Although not reported to be associated with the prognosis of AML patients, ADGRG1, NDST1, FHL1, FAM124B, NYNRIN and CALCRL had been reported to be related with several other cancers and might be potential novel prognostic factors of AML.…”

Section: Discussionmentioning

confidence: 99%

Development and validation of a 10‐gene prognostic signature for acute myeloid leukaemia

Yang

Shang

et al. 2020

J Cellular Molecular Medi

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Acute myeloid leukaemia (AML) is haematologic malignancy with high heterogeneity, characterized by uncontrolled proliferation of myeloid progenitor cells gradually replacing the normal haematopoietic function of bone marrow. With the continuous exploration and research at the cellular and molecular level on the pathogenesis of AML, the choice of novel treatment modalities has surged over the past few years, including targeted small-molecule inhibitors, antibody-drug conjugate, tumour-targeted immunotherapy and so on. 1,2 The prognosis of majority of young AML patients has improved, and most patients have access to complete remission. However, more than half of young adult patients and approximately 90% of older patients still die of their diseases. 3 Hence, a reliable prognostic Abstract Acute myeloid leukaemia (AML) is the most common type of adult acute leukaemia and has a poor prognosis. Thus, optimal risk stratification is of greatest importance for reasonable choice of treatment and prognostic evaluation. For our study, a total of 1707 samples of AML patients from three public databases were divided into meta-training, meta-testing and validation sets. The meta-training set was used to build risk prediction model, and the other four data sets were employed for validation. By log-rank test and univariate COX regression analysis as well as LASSO-COX, AML patients were divided into high-risk and low-risk groups based on AML risk score (AMLRS) which was constituted by 10 survival-related genes. In meta-training, meta-testing and validation sets, the patient in the low-risk group all had a significantly longer OS (overall survival) than those in the high-risk group (P < .001), and the area under ROC curve (AUC) by time-dependent ROC was 0.5854-0.7905 for 1 year, 0.6652-0.8066 for 3 years and 0.6622-0.8034 for 5 years. Multivariate COX regression analysis indicated that AMLRS was an independent prognostic factor in four data sets. Nomogram combining the AMLRS and two clinical parameters performed well in predicting 1-year, 3-year and 5-year OS. Finally, we created a webbased prognostic model to predict the prognosis of AML patients (https://tcgi.shiny apps.io/amlrs_nomog ram/). K E Y W O R D Sacute myeloid leukaemia, gene expression profiling, nomogram, prognosis, signature | 4511 YANG et Al.stratification system which can be applied to clinical risk evaluation is of high importance for the choice of therapy and follow-up in AML patients.Whether it is an established classification system, such as the French-American-British (FAB) classification system in 1976, 4 WorldHealth Organization (WHO) classification in 2008 5 and 2016 6 incorporating genetic information, or prognostic factors, for instance, clinical factors including mounting age and poor performance status, 7 cytogenetic changes 8 and gene mutation, 9 all have their downsides for risk stratification, such as the insufficiency of generalization capacity, the uncertainty in the accuracy of prediction. Hence, recently increasing sight has turned to studies o...

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GPR56/ADGRG1 Inhibits Mesenchymal Differentiation and Radioresistance in Glioblastoma

Cited by 58 publications

References 69 publications

Adhesion G protein–coupled receptors—Candidate metabotropic mechanosensors and novel drug targets

Adhesion G protein–coupled receptors—Candidate metabotropic mechanosensors and novel drug targets

Elevation of CXCL1 indicates poor prognosis and radioresistance by inducing mesenchymal transition in glioblastoma

Development and validation of a 10‐gene prognostic signature for acute myeloid leukaemia

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