Regulatory role of p53 in cancer metabolism via SCO2 and TIGAR in human breast cancer

Won, Kyu Yeoun; Lim, Sung‐Jig; Kim, Gou Young; Kim, Youn Wha; Han, Sun-Hee; Song, Jeong Yoon; Lee, Dong-Ki

doi:10.1016/j.humpath.2011.04.021

Cited by 97 publications

(97 citation statements)

References 24 publications

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“…A high expression of TIGAR was noted in almost 75% of the examined breast tumors (47). To assess whether TIGAR may be regulated in glioblastoma tumors, an in silico analysis was performed with data from (48), using the Oncomine database, a cancer microarray data- base allowing gene expression analysis in different tumor types from genome-wide expression analyses of patient material.…”

Section: Resultsmentioning

confidence: 99%

Tp53-induced Glycolysis and Apoptosis Regulator (TIGAR) Protects Glioma Cells from Starvation-induced Cell Death by Up-regulating Respiration and Improving Cellular Redox Homeostasis

Wanka

Steinbach

Rieger

2012

Journal of Biological Chemistry

142

145

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Background: Tp53-induced glycolysis and apoptosis regulator (TIGAR) is a p53 target gene that has been shown to inhibit glycolysis and activate the pentose phosphate pathway (PPP). Results: TIGAR regulates mitochondrial respiration and intracellular reactive oxygen species (ROS) levels. Conclusion: TIGAR improves cellular redox homeostasis. Significance: TIGAR may be a target for metabolic therapies aiming to enhance tumor cell sensitivity toward hypoxia.

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Section: Resultsmentioning

confidence: 99%

Tp53-induced Glycolysis and Apoptosis Regulator (TIGAR) Protects Glioma Cells from Starvation-induced Cell Death by Up-regulating Respiration and Improving Cellular Redox Homeostasis

Wanka

Steinbach

Rieger

2012

Journal of Biological Chemistry

142

145

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“…For example, at low levels of oxidative stress, p53 activates antioxidant genes such as sestrin and glutathione peroxidase (1,6,16). Additionally, p53 induces the expression of TP53-induced glycolysis and apoptosis regulator, which slows glycolysis and promotes the production of NADPH to decrease ROS levels (50). Moreover, p53 suppresses the expression of phosphoglycerate mutase (PGM), which diminishes mitochondrial oxidative respiration and thus attenuates ROS generation (24).…”

Section: Discussionmentioning

confidence: 99%

mTOR plays a critical role in p53-induced oxidative kidney cell injury in HIVAN

Rai

Plagov

Lan

et al. 2013

American Journal of Physiology-Renal Physiology

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“…The concept of Warburg effect depict that cancer cells preferentially utilize the glycolytic pathway to produce ATP even in the presence of oxygen, thus the ability of TIGAR to inhibit cell glycolysis seems to be harmful for cancer cell survival. However, a number of recent studies have reported that TIGAR expression was significantly elevated in human cancers such as glioblastoma (7), invasive breast cancers (8), and colorectal cancers (unpublished observations). The question that urgently needs to be addressed is why cancer cells need more TIGAR if their survival is dependent on glycolysis?…”

Section: Introductionmentioning

confidence: 97%

TIGAR Has a Dual Role in Cancer Cell Survival through Regulating Apoptosis and Autophagy

Xie

et al. 2014

Cancer Research

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The p53-induced glycolysis and apoptosis regulator (TIGAR) inhibits glycolysis, resulting in higher intracellular NADPH, lower reactive oxygen species (ROS) and autophagy activity. In this study, we investigated whether TIGAR might exert dual impacts on cancer cell survival based on its ability to inhibit both apoptosis and autophagy. In liver or lung cancer cells treated with the anticancer drug epirubicin, TIGAR levels increased in a dose-and time-dependent manner. TIGAR silencing enhanced epirubicin-induced elevations in ROS levels and apoptosis rates, in a manner that was blocked by ectopic addition of NADPH or N-acetyl cysteine. These findings were correlated with reduced tumorigenicity and increased chemosensitivity in mouse xenograft tumor assays. In parallel, TIGAR silencing also enhanced the epirubicin-induced activation of autophagy, in a manner that was also blocked by ectopic addition of NADPH. Notably, TIGAR silencing also licensed epirubicin-mediated inactivation of the mTOR pathway, suggesting TIGAR also exerted a negative impact on autophagy. However, genetic or pharmacologic inhibition of autophagy increased epirubicin-induced apoptosis in TIGAR-silenced cells. Overall, our results revealed that TIGAR inhibits both apoptosis and autophagy, resulting in a dual impact on tumor cell survival in response to tumor chemotherapy. Cancer Res; 74(18); 5127-38. Ó2014 AACR.

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Regulatory role of p53 in cancer metabolism via SCO2 and TIGAR in human breast cancer

Cited by 97 publications

References 24 publications

Tp53-induced Glycolysis and Apoptosis Regulator (TIGAR) Protects Glioma Cells from Starvation-induced Cell Death by Up-regulating Respiration and Improving Cellular Redox Homeostasis

Tp53-induced Glycolysis and Apoptosis Regulator (TIGAR) Protects Glioma Cells from Starvation-induced Cell Death by Up-regulating Respiration and Improving Cellular Redox Homeostasis

mTOR plays a critical role in p53-induced oxidative kidney cell injury in HIVAN

TIGAR Has a Dual Role in Cancer Cell Survival through Regulating Apoptosis and Autophagy

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