Glut1 expression in T1 and T2 stage colorectal carcinomas

Sakashita, Masanori; Aoyama, Nobuo; Minami, Rieko; Maekawa, Satoshi; Kuroda, Kohei; Shirasaka, Daisuke; Ichihara, Toshiaki; Kuroda, Yoshikazu; Maeda, Sakan; Kasuga, Masato

doi:10.1016/s0959-8049(00)00371-3

Cited by 87 publications

(17 citation statements)

References 23 publications

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“…Therefore, the study concluded that GLUT1 expression at the deepest site of tumor invasion can be a useful predictor of prognosis in patients with advanced colorectal cancer. Similar results were reported by another group from Japan in a study that also showed a significant correlation between GLUT1 positivity (≥10% of cellular immunostaining) and depth of invasion (45% T1 vs. 74% T2, P < 0.01), histologic differentiation (49% well vs. 74% moderately to poorly, P < 0.05), and morphologic type (42% polypoid vs. 73% depressed, P < 0.05) (99). Combining the results of these studies suggests that GLUT1-mediated 18 F-FDG accumulation in colon cancer can predict the underlying tumor biology in terms of malignancy potential and prognosis.…”

Section: Colon Cancersupporting

confidence: 86%

¹⁸F-FDG Uptake in Lung, Breast, and Colon Cancers: Molecular Biology Correlates and Disease Characterization

Jadvar

Alavi²,

Gambhir³

2009

J Nucl Med

200

176

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It is hoped that in the not too distant future, noninvasive imagingbased molecular interrogation and characterization of tumors can improve our fundamental understanding of the dynamic biologic behavior of cancer. For example, the new dimension of diagnostic information that is provided by 18 F-FDG PET has led to improved clinical decision making and management changes in a substantial number of patients with cancer. In this context, the aim of this review is to bring together and summarize the current data on the correlation between the underlying molecular biology and the clinical observations of tumor 18 F-FDG accumulation in 3 major human cancers: lung, breast, and colon.Key Words: molecular biology; molecular imaging; oncology; PET; PET/CT; breast cancer; colon cancer; 18 F-FDG; lung cancer Theemergenceoft he central role of PET with 18 F-FDG for the imaging evaluation of patients with cancer is undeniable. The development of hybrid PET/CT systems, regional distribution centers for 18 F-FDG, rapidly accumulating clinical experience, and improved reimbursement have all contributed to this phenomenal success. 18 F-FDG PET has been used for diagnosis, initial staging, restaging, prediction, and monitoring of treatment response, surveillance, and prognostication in a variety of cancers. The new dimension of diagnostic information that is provided by 18 F-FDG PET has also led to improved clinical decision making and management changes in a substantial number of patients (1-3).18 F-FDG PET is a molecular imaging technique that monitors tissue glucose metabolism. It has long been known that most tumors are hypermetabolic, with increased glucose metabolism (Warburg effect). The underlying mechanism and reason for elevated glucose metabolism in cancers is multifactorial and more complex than it may appear at first glance (4). These factors include but are not limited to tumor-related components (e.g., type and histologic differentiation), biochemical and molecular alterations (e.g., glucose metabolic pathway, hypoxia), and nontumor-related constituents (e.g., inflammation) (5-8). The 2 recent excellent reviews by Gillies et al. and Plathow et al. summarized the current understanding of the phenotype of elevated glucose metabolism in cancers (9,10). In simple terms, it was postulated that the relationship between tumor growth and glucose metabolism may be explained in terms of adaptation to hypoxia through upregulation of glucose transporters (GLUTs) and translocation and increased enzymatic activity of hexokinase. However, energy production by glycolysis is relatively inefficient (2 adenosine triphosphates produced per glucose with glycolysis rather than 30 ATPs produced with complete oxidation) and produces a toxic acidic microenvironment (9,10). It has been proposed that the increased extracellular acid production may be the underlying basis for promoting tumor survival and spread in the context of the 6 hallmarks of cancer-self-sufficiency in growth signals, insensitivity to antigrowth signals, evasion of apopt...

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Section: Colon Cancersupporting

confidence: 86%

¹⁸F-FDG Uptake in Lung, Breast, and Colon Cancers: Molecular Biology Correlates and Disease Characterization

Jadvar

Alavi²,

Gambhir³

2009

J Nucl Med

200

176

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“…2, 44 The overexpression of GLUT1 is correlated to hypoxia, poor prognosis, and drug resistance in CRC. 24, 45, 46, 47 Other reports found a similar relationship between MCT1 and various CRC characteristics including drug resistance, poor prognosis, and hypoxia. 48, 49 However, the most important biological functions of these two proteins are to supply carbohydrates and export the waste lactate to maintain cellular energy homeostasis.…”

Section: Discussionmentioning

confidence: 76%

Oridonin induces autophagy via inhibition of glucose metabolism in p53-mutated colorectal cancer cells

Mai

Xie

et al. 2017

Cell Death Dis

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The Warburg effect is an important characteristic of tumor cells, making it an attractive therapeutic target. Current anticancer drug development strategies predominantly focus on inhibitors of the specific molecular effectors involved in tumor cell proliferation. These drugs or natural compounds, many of which target the Warburg effect and the underlying mechanisms, still need to be characterized. To elucidate the anticancer effects of a natural diterpenoid, oridonin, we first demonstrated the anticancer activity of oridonin both in vitro and in vivo in colorectal cancer (CRC) cells. Then miRNA profiling of SW480 cells revealed those intracellular signaling related to energy supply was affected by oridonin, suggesting that glucose metabolism is a potential target for CRC therapy. Moreover, our results indicated that oridonin induced metabolic imbalances by significantly inhibiting glucose uptake and reducing lactate export through significantly downregulating the protein levels of GLUT1 and MCT1 in vitro and vivo. However, the ATP level in oridonin-treated CRC cells was not decreased when oridonin blocked the glucose supply, indicating that oridonin induced autophagy process, an important ATP source in cancer cells. The observation was then supported by the results of LC3-II detection and transmission electron microscopy analysis, which confirmed the presence of autophagy. Furthermore, p-AMPK was rapidly deactivated following oridonin treatment, resulting in downregulation of GLUT1 and induction of autophagy in the cancer cells. Thus our finding helped to clarify the anticancer mechanisms of oridonin and suggested it could be applied as a glucose metabolism-targeting agent for cancer treatment.

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“…The GLUT1 immunostaining was semiquantified by grading the proportion of cells that were GLUT1-positive, as described previously [11]: grade 0, negative (no positive cells); grade 1, low positive (less than 10% are); grade 2, moderate positive (10-50% positive cells); and grade 3, high positive (more than 50% positive cells). For purposes of statistical analysis, a cut-off value of 10% was adopted.…”

Section: Methodsmentioning

confidence: 99%

The Glycolytic Phenotype is Correlated with Aggressiveness and Poor Prognosis in Invasive Ductal Carcinomas

et al. 2012

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PurposeGlucose uptake and glycolytic metabolism are enhanced in cancer cells, and increased expression of glucose transporter 1 (GLUT1) has also been reported. The aim of this study was to investigate GLUT1 expression in human breast tissues and invasive ductal carcinomas.MethodsWe used tissue microarrays consisting of normal breast tissue, ductal hyperplasia, ductal carcinoma in situ, invasive ductal carcinoma, and lymph node metastases. We examined GLUT1 expression in the microarrays by immunohistochemistry, reviewed the medical records and performed a clinicopathological analysis.ResultsMembranous GLUT1 expression was observed in normal and tumor cells. GLUT1 expression was higher in ductal carcinoma in situ, invasive ductal carcinoma, and lymph node metastasis than in normal tissue and ductal hyperplasia (p=0.002). Of 276 invasive ductal carcinomas, 106 (38.4%) showed GLUT1 expression. GLUT1 expression was correlated with higher histologic grade (p<0.001), larger tumor size (p=0.025), absence of estrogen receptor (p<0.001), absence of progesterone receptor (p<0.001), and triple-negative phenotype (p<0.001). In univariate survival analysis, patients with GLUT1 expression had poorer overall survival and disease-free survival (p=0.017 and p=0.021, respectively, log-rank test). In multivariate survival analysis with the Cox proportional hazards model, GLUT1 expression was an independent prognostic factor of poorer overall survival and disease-free survival (p=0.017 and p=0.019, respectively).ConclusionGLUT1 expression seems to play an important role in malignant transformation, and the glycolytic phenotype in invasive ductal carcinoma may indicate aggressive biological behavior and a worse prognosis.

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Glut1 expression in T1 and T2 stage colorectal carcinomas

Cited by 87 publications

References 23 publications

¹⁸F-FDG Uptake in Lung, Breast, and Colon Cancers: Molecular Biology Correlates and Disease Characterization

¹⁸F-FDG Uptake in Lung, Breast, and Colon Cancers: Molecular Biology Correlates and Disease Characterization

Oridonin induces autophagy via inhibition of glucose metabolism in p53-mutated colorectal cancer cells

The Glycolytic Phenotype is Correlated with Aggressiveness and Poor Prognosis in Invasive Ductal Carcinomas

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Glut1 expression in T1 and T2 stage colorectal carcinomas

Cited by 87 publications

References 23 publications

18F-FDG Uptake in Lung, Breast, and Colon Cancers: Molecular Biology Correlates and Disease Characterization

18F-FDG Uptake in Lung, Breast, and Colon Cancers: Molecular Biology Correlates and Disease Characterization

Oridonin induces autophagy via inhibition of glucose metabolism in p53-mutated colorectal cancer cells

The Glycolytic Phenotype is Correlated with Aggressiveness and Poor Prognosis in Invasive Ductal Carcinomas

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¹⁸F-FDG Uptake in Lung, Breast, and Colon Cancers: Molecular Biology Correlates and Disease Characterization

¹⁸F-FDG Uptake in Lung, Breast, and Colon Cancers: Molecular Biology Correlates and Disease Characterization