The Role of G Protein-coupled Receptor Kinases in Cancer

Yu, Shan; Sun, Lei; Jiao, Yu‐Fei; Lee, Leo Tsz On

doi:10.7150/ijbs.22896

Cited by 53 publications

(42 citation statements)

References 152 publications

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“…GRKs participate in a wide range of cellular physiological and pathological activities and there are increasing evidences indicated that some of which are closely related to the occurrence and progression of tumors [5][6][7] . In the present study, we reported that absent expression of GRK4 in tumors was significantly associated with worse outcomes in patients with HCC (P<0.05).…”

Section: Discussionmentioning

confidence: 99%

“…The expression pattern and function of the GRK family members have been reported differed among various tumors [6,7,24,25] . In HCC, GRK3 was expressed in larger tumors and early-stage diseases, whereas GRK6 was prone to expression in smaller, moderate histological grade and metastatic tumors [9,10] .…”

Section: Grk4 Was Found Frequently Mutated In High Microsatellite Insmentioning

confidence: 99%

“…GRKs are involved in a wide range of cellular physiological and pathological activities by phosphorylation of the activated G protein-coupled receptors(GPCRs) or through non-GPCR phosphorylation [3][4][5] . Certain GRK signaling pathways are closely related to the occurrence and progression of tumors [6,7] .…”

Section: Introductionmentioning

confidence: 99%

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G protein-coupled receptor kinase 4 as a prognostic factor for hepatocellular carcinoma

Luo

Xiao

et al. 2019

Preprint

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BACKGROUND: GRK4 has been the least understood member of the GRKs and its role in cancer has been rarely investigated. We recently reported that GRK4 halts cell cycle progression and induces cellular senescence in HEK293 cells, which involoves in pathways of cellular development, proliferation, and cell death. The present study aimed at assessing the prognostic value of GRK4 in hepatocellular carcinoma (HCC). METHODS: Expression of GRK4 was detected by immunohistochemistry in paired tumor and peritumoral tissues. In total, 126 patients with HCC from Western China were utilized as the training cohort to develop the nomogram. Eighty-nine cases from Eastern China were used to validate the model’s performance. RESULTS: GRK4 was expressed at lower levels in tumors than in peritumoral tissues in both training (p<0.001) and validation cohorts (p<0.001). Tumoral GRK4 intensity score, tumor type and T stage were independent prognostic factors and used to form a nomogram for predicting overall survival, which obtained a good concordance index of 0.82 and 0.77 in training and validation cohort, respectively. In the training cohort, the positive and negative prediction values with the nomogram were 83% and 75%, respectively, and in the validation cohort was 100% and 52%, respectively. Patients with nomogram scores greater than 32 and 78 were considered to have a high risk for OS. CONCLUSIONS: Low GRK4 expression in tumor tissues indicates poor clinical outcomes. The nomogram including tumoral GRK4 expression would improve the predictive accuracy of OS in HCC patients.

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Section: Discussionmentioning

confidence: 99%

Section: Grk4 Was Found Frequently Mutated In High Microsatellite Insmentioning

confidence: 99%

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G protein-coupled receptor kinase 4 as a prognostic factor for hepatocellular carcinoma

Luo

Xiao

et al. 2019

Preprint

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“…GPCRs scaffold many intracellular signaling proteins by different signaling pathways and induce signaling cascades independent of G protein activation—including Wnt, Notch, transforming growth factor-β (TGF-β), and the hedgehog (Hh) pathways—as well as downstream kinases—such as phosphoinositide 3-kinase (PI3K) and mitogen-activated protein kinase (MAPK) [ 6 ]. Additionally, activated GPCRs also interact with GRKs or other receptors, mediating the downstream signal pathway [ 7 ].…”

Section: Structure and Signal Transduction Of G Protein-coupled Rementioning

confidence: 99%

Emerging Roles of G Protein-Coupled Receptors in Hepatocellular Carcinoma

Peng

Sun

et al. 2018

IJMS

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Among a great variety of cell surface receptors, the largest superfamily is G protein-coupled receptors (GPCRs), also known as seven-transmembrane domain receptors. GPCRs can modulate diverse signal-transduction pathways through G protein-dependent or independent pathways which involve β-arrestins, G protein receptor kinases (GRKs), ion channels, or Src kinases under physiological and pathological conditions. Recent studies have revealed the crucial role of GPCRs in the tumorigenesis and the development of cancer metastasis. We will sum up the functions of GPCRs—particularly those coupled to chemokines, prostaglandin, lysophosphatidic acid, endothelin, catecholamine, and angiotensin—in the proliferation, invasion, metastasis, and angiogenesis of hepatoma cells and the development of hepatocellular carcinoma (HCC) in this review. We also highlight the potential avenues of GPCR-based therapeutics for HCC.

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“…GRKs and barrestins may directly affect functioning of non-GPCRs or indirectly regulate non-GPCR signaling. In addition, incoming evidence supports that changes in function and/or expression of GRKs and barrestins may be important in cardiovascular, inflammatory, metabolic, or cancer pathologies (Vroon et al, 2006;Schumacher and Koch, 2017;Steury et al, 2018;Yu et al, 2018). A better understanding of the pathological roles of GRKs and b-arrestins would provide a basis for new therapeutic targets in different human diseases.…”

mentioning

confidence: 98%