Role in Tumor Growth of a Glycogen Debranching Enzyme Lost in Glycogen Storage Disease

Guin, Sunny; Pollard, Courtney; Ru, Yuanbin; Lew, Carolyn R.; Duex, Jason E.; Dancik, Garrett M.; Owens, Charles; Spencer, Andrea; Knight, Scott; Holemon, Heather; Gupta, Sounak; Hansel, Donna E.; Hellerstein, Marc K.; Lorkiewicz, Pawel; Lane, Andrew N.; Fan, Teresa W.‐M.; Theodorescu, Dan

doi:10.1093/jnci/dju062

Cited by 41 publications

(111 citation statements)

References 35 publications

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“…Despite the understanding of AGL in both glycogenolysis and in GSD III, the present authors were the first to report a connection between AGL and bladder cancer (9,12). Analysis of bladder tumors from patients demonstrated that loss of AGL expression (gene and protein) in cancer has been associated with clinically aggressive tumor prognosis and poor patient mortality (9).…”

Section: Involvement Of Glycogen Debranching Enzyme In Bladder Cancermentioning

confidence: 76%

“…Tumor cells expressing low levels of AGL displayed enhanced anchorage independent and dependent growth, while AGL overexpression decreased anchorage independent and dependent growth (9). Further analysis of AGL low tumor cells presented increased production of limit dextrin, or abnormally branched glycogen, similar to patients with GSD III.…”

Section: Agl Glycogen Metabolism and Regulation Of Glycine Synthesismentioning

confidence: 89%

“…To identify new genes responsible for aggressive bladder cancer growth, an in vivo RNA interference library screening was conducted using a whole genome shRNA library (9). This screen identified amylo-α-1,6-glucosidase,4-α-glucanotrans ferase (AGL) as a potential new regulator of bladder cancer growth (9).…”

Section: Identification Of Glycogen Debranching Enzyme (Agl) As a Newmentioning

confidence: 99%

“…This screen identified amylo-α-1,6-glucosidase,4-α-glucanotrans ferase (AGL) as a potential new regulator of bladder cancer growth (9).…”

Section: Identification Of Glycogen Debranching Enzyme (Agl) As a Newmentioning

confidence: 99%

“…Following identifying AGL as a potential regulator of bladder cancer growth from the functional genomic screen, and demonstrating that loss of AGL expression in bladder tumors leads to poor patient outcome, the authors carried out various cell based functional assays to validate whether AGL serves any functional role in bladder cancer (9). Tumor cells expressing low levels of AGL displayed enhanced anchorage independent and dependent growth, while AGL overexpression decreased anchorage independent and dependent growth (9).…”

Section: Agl Glycogen Metabolism and Regulation Of Glycine Synthesismentioning

confidence: 99%

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Involvement of glycogen debranching enzyme in bladder cancer

Weinhaus

Guin

2017

Biomedical Reports

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Abstract. Bladder cancer is the most common malignancy of the urinary system, however the molecular pathways underlying this disease are incompletely understood. To understand new regulators of bladder cancer progression, the authors carried out a functional genomic screen which identified glycogen debranching enzyme (AGL) as a novel regulator of bladder cancer growth. Glycogen debranching enzyme is involved in glycogen breakdown and germline loss of function mutation of this gene leads to glycogen storage disease type III. To the best of the authors' knowledge, the present study is the first to demonstrate that loss of AGL leads to aggressive bladder tumor growth. AGL mRNA and protein expression in bladder tumors serve as a prognostic marker for patients. Interestingly, AGL's participation in regulating tumor growth is independent of its enzymatic function and involvement with glycogen metabolism in general. Detailed metabolomics and transcriptomic analysis indicated that increases in glucose metabolism, glycine synthesis driven by serine hydroxymethyltransferase 2 and increases in hyaluronic acid synthase 2-driven HA synthesis are major contributors of aggressive bladder tumor growth with loss of AGL. However, the detailed mechanism of how AGL regulates the above mentioned metabolic and genetic pathways is unknown and is being investigated. The present review focuses on AGL's involvement in bladder cancer.

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Section: Involvement Of Glycogen Debranching Enzyme In Bladder Cancermentioning

confidence: 76%

Section: Agl Glycogen Metabolism and Regulation Of Glycine Synthesismentioning

confidence: 89%

Section: Identification Of Glycogen Debranching Enzyme (Agl) As a Newmentioning

confidence: 99%

“…This screen identified amylo-α-1,6-glucosidase,4-α-glucanotrans ferase (AGL) as a potential new regulator of bladder cancer growth (9).…”

Section: Identification Of Glycogen Debranching Enzyme (Agl) As a Newmentioning

confidence: 99%

Section: Agl Glycogen Metabolism and Regulation Of Glycine Synthesismentioning

confidence: 99%

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Involvement of glycogen debranching enzyme in bladder cancer

Weinhaus

Guin

2017

Biomedical Reports

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Identification of a glycolysis‐related gene signature associated with clinical outcome for patients with lung squamous cell carcinoma

Zhang

Nian

et al. 2021

Cancer Medicine

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Lung cancer has an exceptionally high incidence and mortality among all tumors worldwide. It is predicted that there would be 228,820 cases newly diagnosed with lung cancer, and 135,720 cases would die from this tumor in 2020, causing a tremendous social burden. 1 Lung squamous cell carcinoma (LUSC) and lung adenocarcinoma constitute the central part of lung cancer and the former accounts for approximately 25%-30% of all lung. In recent years, the survival of patients with advanced lung adenocarcinoma has been dramatically improved due to

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Glucose Metabolism in Cancer: The Warburg Effect and Beyond

Bose

Zhang

2021

Advances in Experimental Medicine and Biology

113

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Otto Warburg observed a peculiar phenomenon in 1924, unknowingly laying the foundation for the field of cancer metabolism. While his contemporaries hypothesized that tumor cells derived the energy required for uncontrolled replication from proteolysis and lipolysis, Warburg instead found them to rapidly consume glucose, converting it to lactate even in the presence of oxygen. The significance of this finding, later termed the Warburg effect, went unnoticed by the broader scientific community at that time. The field of cancer metabolism lay dormant for almost a century awaiting advances in molecular biology and genetics, which would later open the doors to new cancer therapies [2, 3].

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Role in Tumor Growth of a Glycogen Debranching Enzyme Lost in Glycogen Storage Disease

Abstract: Using an in vivo RNA interference screen, we discovered that AGL, a glycogen debranching enzyme, has a biologically and statistically significant role in suppressing human cancer growth.

Cited by 41 publications

References 35 publications

Involvement of glycogen debranching enzyme in bladder cancer

Involvement of glycogen debranching enzyme in bladder cancer

Identification of a glycolysis‐related gene signature associated with clinical outcome for patients with lung squamous cell carcinoma

Glucose Metabolism in Cancer: The Warburg Effect and Beyond

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