Rhophilin-2 Upregulates Glutamine Synthetase by Stabilizing c-Myc Protein and Confers Resistance to Glutamine Deprivation in Lung Cancer

Xiao, Dakai; He, Jiaxi; Guo, Zhihua; He, Huiming; Yang, Shuai; Huang, Liyan; Hui, Pei

doi:10.3389/fonc.2020.571384

Cited by 9 publications

(7 citation statements)

References 40 publications

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“…We speculated that LUAD patients with high risks may promote the progression of LUAD through the activation of the following pathways, leading to poor prognosis: cell cycle, P53 signaling, DNA replication, adhesion junctions, actin cytoskeleton regulation, cancer pathways, and TGF signaling. P53 [ 27 ], TGF-β [ 28 ] and RHPN2 [ 29 ] participate in LUAD occurrence and development.…”

Section: Discussionmentioning

confidence: 99%

Construction of an immune-related lncRNA signature as a novel prognosis biomarker for LUAD

Chen

Shen²,

et al. 2021

Aging

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The tumor immune microenvironment of lung cancer is associated with prognosis and immunotherapy efficacy. Long noncoding RNAs are identified as prognostic biomarkers associated with immune functions. We constructed a signature comprising differentially expressed immune-related lncRNAs to predict the prognosis of patients with lung adenocarcinoma. We established the immune-related lncRNA signature by pairing immune-related lncRNAs regardless of expression level and lung adenocarcinoma patients were divided into high- and low-risk groups. The prognosis of patients in the two groups was significantly different; The immune-related lncRNA signature could serve as an independent lung adenocarcinoma prognostic indicator. The signature correlated negatively with B cell, CD4+ T cell, M2 macrophage, neutrophil, and monocyte immune infiltration. Patients with low risk scores had a higher abundance of immune cells and stromal cells around the tumor. Gene set enrichment analysis showed that samples from low-risk group were more active in the IgA production in intestinal immune network and the T and B cell receptor signaling pathway. High-risk groups had significant involvement of the cell cycle, DNA replication, adherens junction, actin cytoskeleton regulation, pathways in cancer, and TGF-β signaling pathways. High risk scores correlated significantly negatively with high CTLA-4 and HAVCR2 expression and higher median inhibitory concentration of common anti-tumor chemotherapeutics (e.g., cisplatin, paclitaxel, gemcitabine) and targeted therapy (e.g., erlotinib and gefitinib). We identified a reliable immune-related lncRNA lung adenocarcinoma prognosis model, and the immune-related lncRNA signature showed promising clinical prediction value.

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Section: Discussionmentioning

confidence: 99%

Construction of an immune-related lncRNA signature as a novel prognosis biomarker for LUAD

Chen

Shen²,

et al. 2021

Aging

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“…Ectopic overexpression of RHPN2 promotes c-Myc protein stability by phosphorylating the Ser62 site and increasing the expression of c-Myc targeted Gln synthetase, which in turn confers resistance of lung cancer cells to Gln depletion. Analysis of GS expression in clinical samples showed that GS expression was elevated in tumor cells and that high levels of GS were significantly associated with poorer overall survival time in lung adenocarcinoma patients (65). L-Phosphinothricin (glufosinate or 2-amino-4-((hydroxy(methyl) phosphinyl) butyric acid ammonium salt (AHPB) is a structural analogue of glutamate and is a recognized herbicide that takes effects on weeds by inhibiting Gln synthetase.…”

Section: Other Intermediates In Gln Pathwaymentioning

confidence: 99%

Therapeutic Potential of Glutamine Pathway in Lung Cancer

et al. 2022

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Cancer cells tend to obtain the substances needed for their development depending on altering metabolic characteristics. Among the reorganized metabolic pathways, Glutamine pathway, reprogrammed to be involved in the physiological process including energy supply, biosynthesis and redox homeostasis, occupies an irreplaceable role in tumor cells and has become a hot topic in recent years. Lung cancer currently maintains a high morbidity and mortality rate among all types of tumors and has been a health challenge that researchers have longed to overcome. Therefore, this study aimed to clarify the essential role of glutamine pathway played in the metabolism of lung cancer and its potential therapeutic value in the interventions of lung cancer.

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“…For example, some of the most frequent oncogenes in human cancers were found to induce the reprogramming of glutamine metabolism and potentially sensitize tumors to anti-glutaminolysis therapies. This includes aberrations in c-MYC [ 47 , 48 , 49 ], JUN [ 50 ], TP53 [ 41 , 43 ], KRAS [ 23 , 51 , 52 ], RB1 [ 53 ], STK11 [ 51 ], KEAP1 [ 51 , 54 ], IDH1 [ 55 , 56 ], the PI3K/mTOR axis [ 34 ], and FLT3 tyrosine kinase signaling [ 57 ]. Moreover, the involvement of glutamine and GLS in redox homeostasis also makes glutamine a crucial player in the cellular handling of oxidative stress.…”

Section: Cancer Glutaminolysismentioning

confidence: 99%

Therapeutic Targeting of Glutaminolysis as a Novel Strategy to Combat Cancer Stem Cells

Kao

Chuang

Lee

et al. 2022

IJMS

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Rare subpopulations of cancer stem cells (CSCs) have the ability to self-renew and are the primary driving force behind cancer metastatic dissemination and the preeminent hurdle to cancer treatment. As opposed to differentiated, non-malignant tumor offspring, CSCs have sophisticated metabolic patterns that, depending on the kind of cancer, rely mostly on the oxidation of major fuel substrates such as glucose, glutamine, and fatty acids for survival. Glutaminolysis is a series of metabolic reactions that convert glutamine to glutamate and, eventually, α-ketoglutarate, an intermediate in the tricarboxylic acid (TCA) cycle that provides biosynthetic building blocks. These building blocks are mostly utilized in the synthesis of macromolecules and antioxidants for redox homeostasis. A recent study revealed the cellular and molecular interconnections between glutamine and cancer stemness in the cell. Researchers have increasingly focused on glutamine catabolism in their attempt to discover an effective therapy for cancer stem cells. Targeting catalytic enzymes in glutaminolysis, such as glutaminase (GLS), is achievable with small molecule inhibitors, some of which are in early-phase clinical trials and have promising safety profiles. This review summarizes the current findings in glutaminolysis of CSCs and focuses on novel cancer therapies that target glutaminolysis in CSCs.

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Rhophilin-2 Upregulates Glutamine Synthetase by Stabilizing c-Myc Protein and Confers Resistance to Glutamine Deprivation in Lung Cancer

Cited by 9 publications

References 40 publications

Construction of an immune-related lncRNA signature as a novel prognosis biomarker for LUAD

Construction of an immune-related lncRNA signature as a novel prognosis biomarker for LUAD

Therapeutic Potential of Glutamine Pathway in Lung Cancer

Therapeutic Targeting of Glutaminolysis as a Novel Strategy to Combat Cancer Stem Cells

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