High expression of GNA13 is associated with poor prognosis in hepatocellular carcinoma

Xu, Yi; Rong, Jian; Duan, Shiyu; Li, Yin; Peng, Baogang; Yi, Bin; Zheng, Zhaohui; Gao, Ying; Wang, Kebing; Miao, Yun; Weng, Hui-Wen; Zhang, Jiaxing

doi:10.1038/srep35948

Cited by 17 publications

(19 citation statements)

References 35 publications

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“…GNA13 has recently been shown to be highly expressed in a variety of human malignancies, including gastric carcinoma, liver carcinoma, and lymphoma, and is positively correlated with tumor progression. 15,[20][21][22] However, the role of GNA13 in CRC is unknown. Our study showed that the upregulation of GNA13 in CRC tissues was related to an exacerbated tumor grade and shorter survival.…”

Section: Discussionmentioning

confidence: 99%

Retracted: GNA13 promotes tumor growth and angiogenesis by upregulating CXC chemokines via the NF‐κB signaling pathway in colorectal cancer cells

et al. 2018

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GNA13 has been found overexpressed in various types of cancer, which is related to tumor metastasis and progression. However, the biological functions of GNA13 in colorectal cancer (CRC) progression remain unclear. This study aimed to explore the role of GNA13 in CRC and investigate the mechanism of how GNA13 promotes tumor growth. Interestingly, our findings showed that GNA13 is commonly upregulated in CRC, where these events are associated with a worse histologic grade and poor survival. Increased expression levels of GNA13 promoted cell growth, migration, invasion, and epithelial‐mesenchymal transition, whereas GNA13 silencing abrogated these malignant phenotypes. In addition, overexpressing GNA13 in cancer cells increased the levels of the chemokines CXCL1, CXCL2, and CXCL4, which contributed to CRC proliferation and colony formation. Moreover, our mechanistic investigations suggest that the NF‐κB/p65 signaling pathway was activated by the increase in GNA13 levels. Inhibiting the NF‐κB/p65 pathway with an inhibitor decreased GNA13‐induced migration, invasion and CXCL chemokine level increases, indicating the critical role of NF‐κB/p65 signaling in mediating the effects of GNA13 in CRC. Together, these results demonstrate a key role of GNA13 overexpression in CRC that contributes to malignant behavior in cancer cells, at least in part through stimulating angiogenesis and increasing the levels of the NF‐κB‐dependent chemokines CXCL1, CXCL2, and CXCL4.

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Section: Discussionmentioning

confidence: 99%

Retracted: GNA13 promotes tumor growth and angiogenesis by upregulating CXC chemokines via the NF‐κB signaling pathway in colorectal cancer cells

et al. 2018

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“…Their downstream signaling cascades are transduced through G‐Alpha12 (GNA12) and G‐Alpha13 (GNA13) subunits constituting the subfamily of heterotrimeric G‐proteins. Indeed, invasion and metastasis have been attributed to GNA proteins in many cancer types . Some findings reported that GNA13 is highly upregulated in the aggressive form of breast cancer cells and restoration of GNA13 activity has been shown to enhance the progression and invasion characteristics of prostate and gastric cancer cells .…”

Section: Discussionmentioning

confidence: 99%

Moonlighting Proteins and Cardiopathy in the Spatial Response of MCF‐7 Breast Cancer Cells to Tamoxifen

Alkhanjaf

Raggiaschi

Crawford

et al. 2019

Proteomics Clinical Apps

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BackgroundThe purpose of this study is to apply quantitative high‐throughput proteomics methods to investigate dynamic aspects of protein changes in nucleocytoplasmic distribution of proteins and of total protein abundance for MCF‐7 cells exposed to tamoxifen (Tam) in order to reveal the agonistic and antagonistic roles of the drug.Experimental designThe MS‐based global quantitative proteomics with the analysis of fractions enriched in target subcellular locations is applied to measure the changes in total abundance and in the compartmental abundance/distribution between the nucleus and cytoplasm for several thousand proteins differentially expressed in MCF‐7 cells in response to Tam stimulation.ResultsThe response of MCF‐7 cells to the Tam treatment shows significant changes in subcellular abundance rather than in their total abundance. The bioinformatics study reveals the relevance of moonlighting proteins and numerous pathways involved in Tam response of MCF‐7 including some of which may explain the agonistic and antagonistic roles of the drug.ConclusionsThe results indicate possible protective role of Tam against cardiovascular diseases as well as its involvement in G‐protein coupled receptors pathways that enhance breast tissue proliferation.

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“…Gα 12/13 , also known as gep proto-oncogenes, are often overexpressed in cancers, including breast 12 , prostate 13 , and liver 14 cancers. They serve as prognostic factors, and high expression of Gα 12/13 is associated with poor prognosis for patients 15 , 16 . The members of the Gα 12/13 family have been recently identified as direct or indirect regulators of systemic energy metabolism.…”

Section: Gpcr–g Protein Pathways In Metabolic Diseasesmentioning

confidence: 99%

Gα12/13 signaling in metabolic diseases

et al. 2020

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As the key governors of diverse physiological processes, G protein-coupled receptors (GPCRs) have drawn attention as primary targets for several diseases, including diabetes and cardiovascular disease. Heterotrimeric G proteins converge signals from~800 members of the GPCR family. Among the members of the G protein α family, the Gα 12 family members comprising Gα 12 and Gα 13 have been referred to as gep oncogenes. Gα 12/13 levels are altered in metabolic organs, including the liver and muscles, in metabolic diseases. The roles of Gα 12/13 in metabolic diseases have been investigated. In this review, we highlight findings demonstrating Gα 12/13 amplifying or dampening regulators of phenotype changes. We discuss the molecular basis of G protein biology in the context of posttranslational modifications to heterotrimeric G proteins and the cell signaling axis. We also highlight findings providing insights into the organ-specific, metabolic and pathological roles of G proteins in changes associated with specific cells, energy homeostasis, glucose metabolism, liver fibrosis and the immune and cardiovascular systems. This review summarizes the currently available knowledge on the importance of Gα 12/13 in the physiology and pathogenesis of metabolic diseases, which is presented according to the basic understanding of their metabolic actions and underlying cellular and molecular bases. GPCR-G protein pathways in metabolic diseases Metabolic syndrome has been a serious health issue in the 21st century. It is a cluster of risk factors that can lead to cardiovascular diseases, diabetes, and stroke. Insulin resistance is the major factor that induces metabolic syndrome. It has been estimated that 642 million people will have type 2 diabetes by 2040 1. The G protein-coupled receptor (GPCR) family is the largest membrane receptor family and serves as an attractive drug target. Currently, FDA-approved drugs, which account for approximately one-third of all drugs, target more than 100 GPCRs 2. The glucagon-like peptide-1 (GLP-1) receptor, a member of the glucagon receptor family of GPCRs, is a metabolic syndrome-associated drug target. GLP-1 receptor agonists are used for glycemic control in patients with type 2 diabetes mellitus 3. Because of its weight-loss effects, liraglutide (Saxenda TM) has become the first GLP-1 receptor agonist approved for the treatment of obesity 4. Many GPCRs are pivotal sensors of energy metabolism. Some GPCRs are activated by energy metabolites or substrates, such as fatty acids, nucleotides, saccharides, hydroxycarboxylic acids, and citric acid cycle intermediates 5. GPCRs activated by fatty acid-derived lipids have been proposed as antidiabetic drugs 6. For example, the beneficial effect of omega-3 fatty acids is mediated by GPR120, also known as free fatty acid receptor 4. GPR120 is an attractive therapeutic target for the treatment of type 2 diabetes. GPR120-selective agonists improve insulin resistance and chronic inflammation and are currently under investigation for possible drug development...

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High expression of GNA13 is associated with poor prognosis in hepatocellular carcinoma

Cited by 17 publications

References 35 publications

Retracted: GNA13 promotes tumor growth and angiogenesis by upregulating CXC chemokines via the NF‐κB signaling pathway in colorectal cancer cells

Retracted: GNA13 promotes tumor growth and angiogenesis by upregulating CXC chemokines via the NF‐κB signaling pathway in colorectal cancer cells

Moonlighting Proteins and Cardiopathy in the Spatial Response of MCF‐7 Breast Cancer Cells to Tamoxifen

Gα12/13 signaling in metabolic diseases

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