ME1 Regulates NADPH Homeostasis to Promote Gastric Cancer Growth and Metastasis

Lü, Yun; Ju, Huai-Qiang; Liu, Zexian; Chen, Dong Liang; Wang, Yun; Zhao, Qi; Wu, Qi; Zeng, Zhao Lei; Qiu, Hai Bo; Hu, Pei; Wang, Zhi Qiang; Zhang, Dong Sheng; Wang, Feng; Xu, Rui‐Hua

doi:10.1158/0008-5472.can-17-3155

Cited by 104 publications

(88 citation statements)

References 35 publications

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“…Furthermore, aberrant ME1 gene expression was associated with poor prognosis of gastric cancer. Exploring the therapeutic potential of ME1 in cell line-based as well as patient derived xenograft models, gene silencing of ME1 significantly suppressed tumor growth increasing cell apoptosis [129]. ME1-repressed cells show a decreased tolerance to low-glucose condition and diminished migration and invasion of nasopharyngeal cancer cells [130].…”

Section: Citrate/pyruvate Shuttlementioning

confidence: 99%

TCA Cycle Rewiring as Emerging Metabolic Signature of Hepatocellular Carcinoma

Todisco

Convertini

Iacobazzi

et al. 2019

Cancers

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Hepatocellular carcinoma (HCC) is a common malignancy. Despite progress in treatment, HCC is still one of the most lethal cancers. Therefore, deepening molecular mechanisms underlying HCC pathogenesis and development is required to uncover new therapeutic strategies. Metabolic reprogramming is emerging as a critical player in promoting tumor survival and proliferation to sustain increased metabolic needs of cancer cells. Among the metabolic pathways, the tricarboxylic acid (TCA) cycle is a primary route for bioenergetic, biosynthetic, and redox balance requirements of cells. In recent years, a large amount of evidence has highlighted the relevance of the TCA cycle rewiring in a variety of cancers. Indeed, aberrant gene expression of several key enzymes and changes in levels of critical metabolites have been observed in many solid human tumors. In this review, we summarize the role of the TCA cycle rewiring in HCC by reporting gene expression and activity dysregulation of enzymes relating not only to the TCA cycle but also to glutamine metabolism, malate/aspartate, and citrate/pyruvate shuttles. Regarding the transcriptional regulation, we focus on the link between NF-κB-HIF1 transcriptional factors and TCA cycle reprogramming. Finally, the potential of metabolic targets for new HCC treatments has been explored.

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Section: Citrate/pyruvate Shuttlementioning

confidence: 99%

TCA Cycle Rewiring as Emerging Metabolic Signature of Hepatocellular Carcinoma

Todisco

Convertini

Iacobazzi

et al. 2019

Cancers

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“…Long noncoding RNAs (lncRNAs) are suggested to be involved in metabolic reprogramming, but the mechanisms remain elusive 2,3 . Our recent studies investigated the roles of metabolic reprogramming in promoting glycolysis and redox hemostasis [4][5][6][7] . The roles of lncRNAs in metabolism remodeling and the underlying mechanisms have thus attracted our interest.…”

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confidence: 99%

Long noncoding RNA AGPG regulates PFKFB3-mediated tumor glycolytic reprogramming

et al. 2020

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Tumor cells often reprogram their metabolism for rapid proliferation. The roles of long noncoding RNAs (lncRNAs) in metabolism remodeling and the underlying mechanisms remain elusive. Through screening, we found that the lncRNA Actin Gamma 1 Pseudogene (AGPG) is required for increased glycolysis activity and cell proliferation in esophageal squamous cell carcinoma (ESCC). Mechanistically, AGPG binds to and stabilizes 6-phosphofructo-2-kinase/fructose-2,6-biphosphatase 3 (PFKFB3). By preventing APC/C-mediated ubiquitination, AGPG protects PFKFB3 from proteasomal degradation, leading to the accumulation of PFKFB3 in cancer cells, which subsequently activates glycolytic flux and promotes cell cycle progression. AGPG is also a transcriptional target of p53; loss or mutation of TP53 triggers the marked upregulation of AGPG. Notably, inhibiting AGPG dramatically impaired tumor growth in patient-derived xenograft (PDX) models. Clinically, AGPG is highly expressed in many cancers, and high AGPG expression levels are correlated with poor prognosis, suggesting that AGPG is a potential biomarker and cancer therapeutic target.

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“…In malignancies, ME1 overexpression correlated with unfavorable prognosis in HCC patients by EMT induction [137]. In addition, ME1 is associated with tumor growth, lung metastasis, peritoneal dissemination, and shorter overall and disease-free survival in gastric cancer cases [138]. Our experimental data suggested that ME1 promotes cancer progression by increasing lactate fermentation, maintaining redox status, acquiring stemness and EMT phenotype, and promoting tumor growth and invasion in OSCC cells [74].…”

Section: Novel Prognosticators Of Osccmentioning

confidence: 98%

Hallmarks of Cancer-Related Newly Prognostic Factors of Oral Squamous Cell Carcinoma

Sasahira

Kirita

2018

IJMS

204

184

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Head and neck cancer, including oral squamous cell carcinoma (OSCC), is the sixth leading malignancy worldwide. OSCC is an aggressive tumor and its prognosis has exhibited little improvement in the last three decades. Comprehensive elucidation of OSCC’s molecular mechanism is imperative for early detection and treatment, improving patient survival. Based on broadly accepted notions, OSCC arises from multiple genetic alterations caused by chronic exposure to carcinogens. In 2011, research revealed 10 key alterations fundamental to cancer cell development: sustaining proliferative signaling, evading growth suppressors, avoiding immune destruction, activating invasion and metastasis, tumor-promoting inflammation, enabling replicative immortality, inducing angiogenesis, genome instability and mutation, resisting cell death, and deregulating energetics. This review describes molecular pathological findings on conventional and novel hallmarks of OSCC prognostic factors. In addition, the review summarizes the functions and roles of several molecules as novel OSCC prognosticators.

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ME1 Regulates NADPH Homeostasis to Promote Gastric Cancer Growth and Metastasis

Cited by 104 publications

References 35 publications

TCA Cycle Rewiring as Emerging Metabolic Signature of Hepatocellular Carcinoma

TCA Cycle Rewiring as Emerging Metabolic Signature of Hepatocellular Carcinoma

Long noncoding RNA AGPG regulates PFKFB3-mediated tumor glycolytic reprogramming

Hallmarks of Cancer-Related Newly Prognostic Factors of Oral Squamous Cell Carcinoma

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