Cancer cell adaptation to hypoxia involves a HIF‐GPRC5A‐YAP axis

Greenhough, Alexander; Bagley, Clare; Heesom, Kate J; Gurevich, David; Gay, David M.; Bond, Mark; Collard, Tracey J; Paraskeva, C; Martin, Paul; Sansom, Owen J.; Malik, Karim; Williams, Ann C.

doi:10.15252/emmm.201708699

Cited by 78 publications

(67 citation statements)

References 52 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…GPRC5A is highly expressed in colorectal cancer (CRC), and elevated GPRC5A expression is significantly associated with inferior prognosis [ 87 , 88 ]. In addition, liquid chromatography analysis demonstrates that GPRC5A expression is lower in polyps than in metastatic and non-metastatic CRC samples, suggesting that GPRC5A may serve as a biomarker to differentiate CRC from normal tissues [ 89 ].…”

Section: Gprc5a and Its Role In Human Cancermentioning

confidence: 99%

“…What is more, GPRC5A deficiency reduces cell proliferation and promotes cell apoptosis in vitro and inhibits tumorigenesis of a colitis-associated cancer model in vivo . Furthermore, GPRC5A can be induced by hypoxia, regulates the NF- κ B-mediated expression of Vanin-1 (a key enzyme of cysteamine generation), and influences the reactive oxygen levels contributing to tumor progression [ 88 , 90 ].…”

Section: Gprc5a and Its Role In Human Cancermentioning

confidence: 99%

See 1 more Smart Citation

GPRC5A: An Emerging Biomarker in Human Cancer

Jiang

et al. 2018

BioMed Research International

View full text Add to dashboard Cite

Aberrant expression of G protein-coupled receptors (GPCRs) is frequently associated with tumorigenesis. G Protein-coupled receptor class C group 5 member A (GPRC5A) is a member of the GPCR superfamily, is expressed preferentially in lung tissues, and is regulated by various entities at multiple levels. GPRC5A exerts a tumor suppressive role in lung cancer and GPRC5A deletion promotes lung tumor initiation and progression. Recent advances have highlighted that GPRC5A dysregulation is found in various human cancers and is related to many tumor-associated signaling pathways, including the cyclic adenosine monophosphate (cAMP), nuclear factor (NF)-κB, signal transducer and activator of transcription (STAT) 3, and focal adhesion kinase (FAK)/Src signaling. This review aimed to summarize our updated view on the biology and regulation of GPRC5A, its expression in human cancers, and the linked signaling pathways. A better comprehension of the underlying cellular and molecular mechanisms of GPRC5A will provide novel insights into its potential diagnostic and therapeutic value.

show abstract

Section: Gprc5a and Its Role In Human Cancermentioning

confidence: 99%

Section: Gprc5a and Its Role In Human Cancermentioning

confidence: 99%

GPRC5A: An Emerging Biomarker in Human Cancer

Jiang

et al. 2018

BioMed Research International

View full text Add to dashboard Cite

show abstract

“…[ 274 ] Hypoxia was reported to repress LATS1/2 gene expression to promote YAP activation during endometriosis, [ 275 ] while another group found that hypoxia induced expression of an orphan GPCR, the GPCR5A gene, to activate YAP in colonic epithelial cells. [ 276 ] YAP was also reported to maintain HIF‐1alpha expression. [ 277 ] Others reported that Hypoxia promoted YAP nuclear localization via direct YAP‐HIF‐1alpha binding.…”

Section: Introductionmentioning

confidence: 99%

YAP/TAZ: Drivers of Tumor Growth, Metastasis, and Resistance to Therapy

2020

View full text Add to dashboard Cite

The transcriptional co-activators YAP (or YAP1) and TAZ (or WWTR1) are frequently activated during the growth and progression of many solid tumors, including lung, colorectal, breast, pancreatic, and liver carcinomas as well as melanoma and glioma. YAP/TAZ bind to TEAD-family co-activators to drive cancer cell survival, proliferation, invasive migration, and metastasis. YAP/TAZ activation may also confer resistance to chemotherapy, radiotherapy, or immunotherapy. YAP-TEAD cooperates with the RAS-induced AP-1 (FOS/JUN) transcription factor to drive tumor growth and cooperates with MRTF-SRF to promote activation of cancer-associated fibroblasts, matrix stiffening, and metastasis. The key upstream repressor of YAP/TAZ activation is the Hippo (MST1/2-LATS1/2) pathway and the key upstream activators are mechanically induced Integrin-SRC and E-cadherin-AJUBA/TRIP6/LIMD1, growth factor induced PI3K-AKT, and inflammation-induced G-protein coupled receptor (GPCR) signals, all of which antagonize the Hippo pathway. In this review, strategies to target YAP/TAZ activity in cancer are discussed along with the prospects for synergy with established pillars of cancer therapy.

show abstract

“…Interestingly, GPRC5A has been identified as a novel hypoxia-induced protein that functions to protect cancer cells from apoptosis during oxygen deprivation and was found to be upregulated in colorectal cancers. Mechanistically, GPRC5A acts via the Hippo pathway effector YAP 48 . However, in non-small cell lung carcinoma (NSCLC), GPRC5A is expressed as much lower levels than in the corresponding noncancerous tissues and was associated to a worse prognosis 46 .…”

Section: Discussionmentioning

confidence: 99%

A multi-layered systems approach for renal cell carcinoma

Rudewicz

Souleyreau

et al. 2020

Preprint

View full text Add to dashboard Cite

Acknowledgments:This work was supported by grants from the PlanCancer («Systems Biology of Renal Cell Carcinoma using an Experimental RCC model» (C18005GS, SystemsRCC)) and from the university Bordeaux (G2P project) to AB. LC and AE were supported by post-doctoral fellowships from the Region "Nouvelle Aquitaine". The Crispr/cas9 construct was gratefully provided by Michel Tremblay (Goodman Cancer Center, McGill, University). The authors would like to thank the lentiviral production plateform Vect'UB for EGFP lentivirus, the "service commun des animaleries" for animal production and housing, and the Bordeaux Imaging Center (BIC). 2 AbstractIn order to discover molecular pathways and players in renal cancer development and metastasis, we developed a mouse model to generate sequentially more aggressive and specialized cell lines. Multiple cell lines for primary tumor growth, survival in the blood circulation and lung metastasis or metastatic spread from the primary tumor were generated and analyzed using a multi-layered approach which includes large-scale transcriptome, genome and methylome analyses. Transcriptome and methylome analyses demonstrated distinct clustering in three different groups. Remarkably, DNA sequencing did not show significant genomic variations in the different groups which indicates absence of clonal selection during the in vivo amplification process. Transcriptome analysis revealed several markers and signatures of tumor aggressiveness which were validated, at the mRNA and protein level, in patient cohorts from TCGA, local biobanks and clinical trials. This also includes soluble markers. In particular, SAA2 and CFB were highly predictive for survival and tumor progression. Methylome analysis of full-length DNA allowed clustering of the same groups and revealed clinically predictive signatures. We also uncovered IL34 as a key regulator of renal cell carcinoma (RCC) progression which was also functionally validated in vivo, and a mathematical model of IL34-dependent primary tumor growth and metastasis development was provided. These results indicate that such multilayered analysis in a RCC animal model leads to meaningful results that are of translational significance. 3

show abstract

Cancer cell adaptation to hypoxia involves a HIF‐GPRC5A‐YAP axis

Cited by 78 publications

References 52 publications

GPRC5A: An Emerging Biomarker in Human Cancer

GPRC5A: An Emerging Biomarker in Human Cancer

YAP/TAZ: Drivers of Tumor Growth, Metastasis, and Resistance to Therapy

A multi-layered systems approach for renal cell carcinoma

Contact Info

Product

Resources

About