Expression level of glutamine synthetase is increased in hepatocellular carcinoma and liver tissue with cirrhosis and chronic hepatitis B

Jiang, Long; Wang, Huaguang; Lang, Z; Wang, Tailing; Ma, Liang; Wang, Bao-en

doi:10.1007/s12072-010-9230-2

Cited by 30 publications

(24 citation statements)

References 28 publications

(29 reference statements)

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“…The liver-type glutaminase 2, which catalyzes the conversion of glutamine to glutamate is almost absent or significantly decreased in human HCC [91]. Consistently, the expression of glutamine synthetase, which catalyzes the opposite reaction, is increased in HCC patients with β-catenin mutations [92][93][94]. Glutamine synthetase is a target gene of β-catenin and overexpression of glutamine synthetase is highly correlated with β-catenin mutations [92], which in turn is related to early-stage HCC [95].…”

Section: Metabolic Alterations In Liver Cancermentioning

confidence: 82%

“…Glutamine synthetase is a target gene of β-catenin and overexpression of glutamine synthetase is highly correlated with β-catenin mutations [92], which in turn is related to early-stage HCC [95]. Moreover, glutamine synthetase expression is correlated with HCC progression [93,96]. Supporting the importance of glutamine metabolism in liver cancer, increased concentrations of glutamate and glutamine have been detected in human HCC in comparison to adjacent normal tissue [97].…”

Section: Metabolic Alterations In Liver Cancermentioning

confidence: 97%

“…Supporting the importance of glutamine metabolism in liver cancer, increased concentrations of glutamate and glutamine have been detected in human HCC in comparison to adjacent normal tissue [97]. Interestingly, glutamine synthethase expression is related to liver regeneration and therefore is observed during cirrhosis (a pre-state of liver cancer) [93,98]. Thus, whether glutamine synthetase expression is a drug target or only a biomarker remains to be determined.…”

Section: Metabolic Alterations In Liver Cancermentioning

confidence: 99%

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Organ-Specific Cancer Metabolism and Its Potential for Therapy

et al. 2015

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KEYWORDS:Cancer metabolism, metabolic therapy, tissue specific metabolism, genetic drivers, epigenetic drivers, microenvironment, Warburg effect, reverse Warburg effect, mixed Warburg effect, triple-negative breast cancer, estrogen receptor positive breast cancer; prostate cancer, liver cancer, gluconeogenesis, fatty acid metabolism, glucose metabolism, glutamine metabolism, serine metabolism, metabolic normalization, metabolic depletion ABSTRACTTargeting the metabolism of cancer cells has the potential to lead to major advances in tumor therapy. Numerous promising metabolic drug targets have been identified. Yet, it has emerged that there is no singular metabolism that defines the oncogenic state of the cell. Rather, the metabolism of cancer cells is a function of the requirements of a tumor. Hence, the tissue of origin, the (epi)genetic drivers, aberrant signaling, and the microenvironment all together define these metabolic requirements. In this chapter we discuss in light of (epi)genetic, signaling, and environmental factors the diversity in cancer metabolism based on triple-negative and estrogen receptor positive breast cancer, early and late stage prostate cancer, and liver cancer. These types of cancer all display distinct and partially opposing metabolic behaviors (e.g. Warburg versus reverse Warburg metabolism). Yet, for each of the cancers their distinct metabolism supports the oncogenic phenotype. Finally, we will assess the therapeutic potential of metabolism based on the concepts of metabolic normalization and metabolic depletion.

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Section: Metabolic Alterations In Liver Cancermentioning

confidence: 82%

Section: Metabolic Alterations In Liver Cancermentioning

confidence: 97%

Section: Metabolic Alterations In Liver Cancermentioning

confidence: 99%

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Organ-Specific Cancer Metabolism and Its Potential for Therapy

et al. 2015

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“…44 Also, cigarette smoking impairs the metabolic conversion of glutamine and therefore promotes a high level of glutamine in lung cancer cells. 45 While high GS and high glutamine levels have been shown to enhance the metastatic potential and rate of tumor recurrence in hepatocellular carcinoma, 46 the prognostic significance of glutamine and its metabolizing enzymes in lung cancer has not been well elucidated. Nonetheless, glutamine is an important molecule required for the normal function of non-neoplastic lungs 47 and plays a significant role in cancer cell growth, protein translation, anaplerosis and macromolecule synthesis.…”

Section: Discussionmentioning

confidence: 99%

Altered Glutamine Metabolism and Therapeutic Opportunities for Lung Cancer

Mohamed¹,

Deng²,

Khuri³

et al. 2014

Clinical Lung Cancer

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Disordered cancer metabolism was described almost a century ago as an abnormal adaptation of cancer cells to glucose utilization especially under hypoxic conditions; the so-called Warburg effect. Greater research interest in this area in the last several decades has led to the recognition of the critical coupling of specific malignant phenotypes such as increased proliferation and resistance to programmed cell death (apoptosis) with altered metabolic handling of key molecules that are essential for normal cellular metabolism. The altered glucose metabolism frequently encountered in cancer cells has been exploited for cancer diagnosis and treatment. More recently, the role of other glycolytic pathway intermediates as well as alternative pathways for energy generation and macromolecular synthesis in cancer cells has become recognized. Especially, the important role of altered glutamine metabolism in the malignant behavior of cancer cells and the potential exploitation of this cellular adaptation for therapeutic targeting has emerged as an important area of cancer research in the last decade. Expectedly, attempts to exploit this understanding for diagnostic and therapeutic ends are running apace with the elucidation of the complex metabolic alterations that accompany neoplastic transformation. Because lung cancer is a leading cause of cancer death with limited curative therapy options, careful elucidation of the mechanism and consequences of disordered cancer metabolism in lung cancer is warranted. This review provides a concise, systematic overview of the current understanding of the role of altered glutamine metabolism in cancer and how these findings intersect with current and future approaches to lung cancer management.

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“…GS is increased in some cancer types like HCCs, where it has been found to be abnormally expressed in the majority of the cases. The high frequency of GS overexpression in HCCs could make this protein a potential biomarker for early diagnosis of HCCs, as already speculated [ 32 ]. Cells expressing high levels of GS should possess a metabolic advantage with respect to cell expressing low levels of GS, since they are less dependent on exogenous glutamine.…”

Section: Alterations Of Glutamine-related Enzymes In Cancer Cellsmentioning

confidence: 80%