Modulation of GLO1 Expression Affects Malignant Properties of Cells

Hutschenreuther, Antje; Bigl, Marina; Hemdan, Nasr Y. A.; Debebe, Tewodros; Gaunitz, Frank; Birkenmeier, Gerd
December 2016
International Journal of Molecular Sciences;Dec2016, Vol. 17 Issue 12, p2133
Academic Journal
The energy metabolism of most tumor cells relies on aerobic glycolysis (Warburg effect) characterized by an increased glycolytic flux that is accompanied by the increased formation of the cytotoxic metabolite methylglyoxal (MGO). Consequently, the rate of detoxification of this reactive glycolytic byproduct needs to be increased in order to prevent deleterious effects to the cells. This is brought about by an increased expression of glyoxalase 1 (GLO1) that is the rate-limiting enzyme of the MGO-detoxifying glyoxalase system. Here, we overexpressed GLO1 in HEK 293 cells and silenced it in MCF-7 cells using shRNA. Tumor-related properties of wild type and transformed cells were compared and key glycolytic enzyme activities assessed. Furthermore, the cells were subjected to hypoxic conditions to analyze the impact on cell proliferation and enzyme activities. Our results demonstrate that knockdown of GLO1 in the cancer cells significantly reduced tumor-associated properties such as migration and proliferation, whereas no functional alterations where found by overexpression of GLO1 in HEK 293 cells. In contrast, hypoxia caused inhibition of cell growth of all cells except of those overexpressing GLO1. Altogether, we conclude that GLO1 on one hand is crucial to maintaining tumor characteristics of malignant cells, and, on the other hand, supports malignant transformation of cells in a hypoxic environment when overexpressed.


Related Articles

  • microRNA-133b downregulation and inhibition of cell proliferation, migration and invasion by targeting matrix metallopeptidase-9 in renal cell carcinoma. DEYAO WU; HUIXING PAN; YUNFENG ZHOU; JIAN ZHOU; YUANFENG FAN; PING QU // Molecular Medicine Reports;2014, Vol. 9 Issue 6, p2491 

    microRNA (miRNA)-133b has been revealed to be downregulated in head and neck/oral, bladder, human non-small cell lung, colorectal and esophageal squamous cell cancer. The present study examined the expression of miR-133b in renal cell carcinoma (RCC) cell lines and the effects of miRNA-133b on...

  • Ion channel gene expression predicts survival in glioma patients. Wang, Rong; Gurguis, Christopher I.; Gu, Wanjun; Ko, Eun A; Lim, Inja; Bang, Hyoweon; Zhou, Tong; Ko, Jae-Hong // Scientific Reports;8/7/2015, p11593 

    Ion channels are important regulators in cell proliferation, migration, and apoptosis. The malfunction and/or aberrant expression of ion channels may disrupt these important biological processes and influence cancer progression. In this study, we investigate the expression pattern of ion channel...

  • Girdin regulates the migration and invasion of glioma cells via the PI3K-Akt signaling pathway. WEIMIN NI; YAN FANG; LEI TONG; ZHAOXUE TONG; FUXIN YI; JIANWU QIU; RUI WANG; XIAOJIE TONG // Molecular Medicine Reports;2015, Vol. 12 Issue 4, p5086 

    Girdin, an actin-binding protein, is associated with cell migration and is expressed at high levels in glioma cells. However, the association between girdin and the development of glioma remains to be elucidated. In the present study, short-hairpin RNA technology was used to silence the gene...

  • Strategies to investigate gene expression and function in granule cells. Savill, Rebecca M.; Scotting, Paul J.; Coyle, Beth // Cerebellum;Dec2005, Vol. 4 Issue 4, p271 

    Studying gene expression in granule cells is a major route to understanding the factors required for many key cellular processes such as specification, proliferation, migration, differentiation, apoptosis, tumour formation and neurodegeneration. A greater understanding of these processes will...

  • miR-141 suppresses proliferation and motility of gastric cancer cells by targeting HDGF. Chen, Bitao; Huang, Tao; Jiang, Jun; Lv, Lei; Li, Hongxing; Xia, Shitao // Molecular & Cellular Biochemistry;Mar2014, Vol. 388 Issue 1/2, p211 

    miR-141 belongs to the miR-200 family, and has been found to be associated with numerous human malignancies; however, its role in gastric cancer (GC) has not been examined in detail. Here, we validated that miR-141 was decreased in GC tissues and cell lines. Forced expression of miR-141...

  • The Scatter Factor Signaling Pathways as Therapeutic Associated Target in Cancer Treatment. Accornero, P.; Pavone, L. M.; Baratta, M. // Current Medicinal Chemistry;Sep2010, Vol. 17 Issue 25, p2699 

    Receptor tyrosine kinases (RTKs) are key regulators of critical cellular processes such as proliferation, differentiation, neo-vascularization, and tissue repair. In addition to their importance in the regulation of normal physiology, aberrant expression of certain RTKs has also been associated...

  • Metastasis-associated phosphatase PRL-2 regulates tumor cell migration and invasion. Wang, Y; Lazo, J S // Oncogene;2/16/2012, Vol. 31 Issue 7, p818 

    The phosphatase of regenerating liver (PRL) family, comprising PRL-1, PRL-2 and PRL-3, is a group of prenylated phosphatases that are candidate cancer biomarkers and therapeutic targets. Although several studies have documented that altered expression of PRL-1 or PRL-3 can influence cell...

  • Differential expression of chemokine receptors and their roles in cancer imaging. Nimmagadda, Sridhar // Frontiers in Oncology;May2012, Vol. 2, p1 

    Chemokine/chemokine receptor interactions play diverse roles in cell migration and homeostasis. Emerging evidence suggests that cancer cells co-opt chemokine networks for survival, proliferation, immune evasion, and metastasis. Most of the chemokine receptors are reported to be involved in tumor...

  • A Class III Semaphorin (Sema3e) Inhibits Mouse Osteoblast Migration and Decreases Osteoclast Formation In Vitro. Hughes, Alun; Kleine-Albers, Jennifer; Helfrich, Miep; Ralston, Stuart; Rogers, Michael // Calcified Tissue International;Feb2012, Vol. 90 Issue 2, p151 

    Originally identified as axonal guidance cues, semaphorins are expressed throughout many different tissues and regulate numerous non-neuronal processes. We demonstrate that most class III semaphorins are expressed in mouse osteoblasts and are differentially regulated by cell growth and...

  • BRG1 expression is increased in human glioma and controls glioma cell proliferation, migration and invasion in vitro. Bai, Jin; Mei, Peng-Jin; Liu, Hui; Li, Chen; Li, Wang; Wu, Yong-Ping; Yu, Zheng-Quan; Zheng, Jun-Nian // Journal of Cancer Research & Clinical Oncology;Jun2012, Vol. 138 Issue 6, p991 

    Purpose: The purposes of our study were to elucidate the role of BRG1 in the development of human glioma and to determine the effect of BRG1 on glioma cell growth, migration and invasion. Methods: Using tissue microarray and immunohistochemistry, we evaluated BRG1 staining in 190 glioma tissues,...


Read the Article


Sorry, but this item is not currently available from your library.

Try another library?
Sign out of this library

Other Topics