Glyoxalase-I Is a Novel Prognosis Factor Associated with Gastric Cancer Progression

Cheng, Wanli; Tsai, Ming-Ming; Tsai, Chung‐Ying; Huang, Ya‐Hui; Chen, Cheng-Yi; Chi, Hsiang-Cheng; Tseng, Yi-Hsin; Chao, Im-Wai; Lin, Wann‐Yin; Wu, Sheng-Ming; Li, Ying; Liao, Chia‐Jung; Lin, Yang-Hsiang; Chung, I-Hsiao; Chen, Wen‐Jone; Lin, Paul; Wang, Chia‐Siu; Lin, Kwang‐Huei

doi:10.1371/journal.pone.0034352

Cited by 46 publications

(44 citation statements)

References 41 publications

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“…Most of the recent studies aimed at the inhibition of GLO1 to induce a toxic MG accumulation effectively showed a decreased tumor growth. These studies generally depicted GLO1 as an amplified and/or overexpressed oncogene and as a bad prognosis marker in different types of malignant tumors (Zhang et al., 2014; Cheng, 2012; Hosoda et al, 2015; Antognelli et al, 2013; Fonseca-Sánchez et al, 2012). On the other hand, a study aimed at functionally identifying tumor suppressor genes in liver cancer identified and validated GLO1 as a tumor suppressor gene which knockdown using shRNAs increased tumor growth in a mouse model (Zender et al, 2008).…”

Section: Discussionmentioning

confidence: 99%

Methylglyoxal, a glycolysis side-product, induces Hsp90 glycation and YAP-mediated tumor growth and metastasis

Nokin

Durieux

Peixoto

et al. 2016

eLife

108

120

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Metabolic reprogramming toward aerobic glycolysis unavoidably induces methylglyoxal (MG) formation in cancer cells. MG mediates the glycation of proteins to form advanced glycation end products (AGEs). We have recently demonstrated that MG-induced AGEs are a common feature of breast cancer. Little is known regarding the impact of MG-mediated carbonyl stress on tumor progression. Breast tumors with MG stress presented with high nuclear YAP, a key transcriptional co-activator regulating tumor growth and invasion. Elevated MG levels resulted in sustained YAP nuclear localization/activity that could be reverted using Carnosine, a scavenger for MG. MG treatment affected Hsp90 chaperone activity and decreased its binding to LATS1, a key kinase of the Hippo pathway. Cancer cells with high MG stress showed enhanced growth and metastatic potential in vivo. These findings reinforce the cumulative evidence pointing to hyperglycemia as a risk factor for cancer incidence and bring renewed interest in MG scavengers for cancer treatment.DOI: http://dx.doi.org/10.7554/eLife.19375.001

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Section: Discussionmentioning

confidence: 99%

Methylglyoxal, a glycolysis side-product, induces Hsp90 glycation and YAP-mediated tumor growth and metastasis

Nokin

Durieux

Peixoto

et al. 2016

eLife

108

120

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“…A previous study from our laboratory showed that downregulation of GLOI inhibited the migration and invasion of breast cancer cells [9]. In another published report, downexpression of GLOI in gastric cancer cells reduced their migration and invasion activities [27]. Moreover, Hiroya et al demonstrated that knockdown of GLOI induced apoptosis in cancer cells [28].…”

Section: Discussionmentioning

confidence: 99%

Blockage of Glyoxalase I Inhibits Colorectal Tumorigenesis and Tumor Growth via Upregulation of STAT1, p53, and Bax and Downregulation of c-Myc and Bcl-2

Chen

Fang

Zhang

et al. 2017

IJMS

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GlyoxalaseI (GLOI) is an enzyme that catalyzes methylglyoxal metabolism. Overexpression of GLOI has been documented in numerous tumor tissues, including colorectal cancer (CRC). The antitumor effects of GLOI depletion have been demonstrated in some types of cancer, but its role in CRC and the mechanisms underlying this activity remain largely unknown. Our purpose was to investigate the antitumor effects of depleted GLOI on CRC in vitro and in vivo. RNA interference was used to deplete GLOI activity in four CRC cell lines. The cells’ proliferation, apoptosis, migration, and invasion were assessed by using the Cell Counting Kit-8, plate colony formation assay, flow cytometry, and transwell assays. Protein and mRNA levels were analyzed by western blot and quantitative real-time PCR (qRT-PCR), respectively. The antitumor effect of GLOI depletion in vivo was investigated in a SW620 xenograft tumor model in BALB/c nude mice. Our results show that GLOI is over-expressed in the CRC cell lines. GLOI depletion inhibited the proliferation, colony formation, migration, and invasion and induced apoptosis of all CRC cells compared with the controls. The levels of signal transducer and activator of transcription 1 (STAT1), p53, and Bcl-2 assaciated X protein (Bax) were upregulated by GLOI depletion, while cellular homologue of avian myelocytomatosis virus oncogene (c-Myc) and B cell lymphoma/lewkmia-2 (Bcl-2) were downregulated. Moreover, the growth of SW620-induced CRC tumors in BALB/c nude mice was significantly attenuated by GLOI depletion. The expression levels of STAT1, p53, and Bax were increased and those of c-Myc and Bcl-2 were decreased in the GLOI-depleted tumors. Our findings demonstrate that GLOI depletion has an antitumor effect through the STAT1 or p53 signaling pathways in CRC, suggesting that GLOI is a potential therapeutic target.

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“…Studies have shown that high expression of GLO1 in gastric cancer promotes tumor cell growth and proliferation, and enhances transcriptional activities of NF-κB and AP-1 [20,21]. Since a positive correlation between the level of GLO1 in prostate cancer tissues and the rate of cell proliferation was found, we considered that GLO1 may represent a risk factor for the development and progression of prostate cancer [22].…”

Section: Role Of Gloi In Tumor Development and Progressionmentioning

confidence: 99%

Glyoxalase I in Tumor Cell Proliferation and Survival and as a Potential Target for Anticancer Therapy

Geng

Ma²,

Zhang³

et al. 2014

Oncol Res Treat

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SummaryGlyoxalase I (GLO1) belongs to the glyoxalase system, which catalyzes the conversion of deleterious methylglyoxal, mainly produced by glycolysis, to non-toxic D-lactate. The expression of GLO1 was up-regulated in tumor tissues with high metabolic rate, whereas inhibition of GLO1 expression led to the accumulation of glyoxal and methylglyoxal, significantly inducing cell damage or apoptosis. This suggests that GLO1 may play an important role in tumor cell proliferation and survival, and may represent a potential therapeutic target for tumors. Moreover, overexpression of GLO1 was associated with multidrug resistance in cancer chemotherapy. This review describes the role of GLO1 in tumor cell proliferation and survival, and the potential of GLO1 as a biomarker for tumor diagnosis and as a target for anticancer drug development.

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Glyoxalase-I Is a Novel Prognosis Factor Associated with Gastric Cancer Progression

Cited by 46 publications

References 41 publications

Methylglyoxal, a glycolysis side-product, induces Hsp90 glycation and YAP-mediated tumor growth and metastasis

Methylglyoxal, a glycolysis side-product, induces Hsp90 glycation and YAP-mediated tumor growth and metastasis

Blockage of Glyoxalase I Inhibits Colorectal Tumorigenesis and Tumor Growth via Upregulation of STAT1, p53, and Bax and Downregulation of c-Myc and Bcl-2

Glyoxalase I in Tumor Cell Proliferation and Survival and as a Potential Target for Anticancer Therapy

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