Variant G6PD levels promote tumor cell proliferation or apoptosis via the STAT3/5 pathway in the human melanoma xenograft mouse model

Hu, Tao; Zhang, Chunhua; Tang, Qiongling; Su, Yanan; Li, Bo; Chen, Long; Zhang, Zheng; Cai, Tianchi; Zhu, Yuechun

doi:10.1186/1471-2407-13-251

Cited by 61 publications

(56 citation statements)

References 42 publications

(47 reference statements)

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“…It has been reported that variant G6PD levels can regulate STAT3 expression. Furthermore, STAT3 has been found to negatively regulate type I IFN-induced antiviral response (22,47). Thus our data and previous findings suggest that silencing of G6PD may increase IFN mRNA through the STAT3 pathway.…”

Section: Discussionsupporting

confidence: 83%

Changes in glucose-6-phosphate dehydrogenase expression results in altered behavior of HBV-associated liver cancer cells

Ding

Yang

et al. 2014

American Journal of Physiology-Gastrointestinal and Liver Physi

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Hepatocellular carcinoma (HCC) is regarded as a major global health care issue, and chronic hepatitis B virus (HBV) infection is considered to be involved in pathogenesis of HCC. To increase knowledge of HCC pathogenesis, as well as discover potential novel molecules for anti-cancer therapy, mass spectrometry and isobaric tag for relative and absolute quantitation (iTARQ) were employed. The differences between nine HBV-related HCC and adjacent non-HCC tissue specimens were studied. In total, 222 proteins were analyzed for differential expression in the two types of samples. Among these proteins, several were further confirmed by immunohistochemical, immunoblotting, and real-time RT-PCR analysis. RNA interference induced downregulation of glucose-6-phosphate dehydrogenase (G6PD) and decreased HBV replication by fivefold by the IFN pathway. Decreased G6PD expression resulted in decreased hepatoma cell migration and invasion in cell culture. In summary, the investigation provides new information on pathogenesis of HBV infection and suggests G6PD as a novel anti-HCC target. G6PD suppression may contribute to treatment strategies for inhibiting tumor progression.

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Section: Discussionsupporting

confidence: 83%

Changes in glucose-6-phosphate dehydrogenase expression results in altered behavior of HBV-associated liver cancer cells

Ding

Yang

et al. 2014

American Journal of Physiology-Gastrointestinal and Liver Physi

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“…Furthermore, STAT3 is required for the activation of proto-oncogenes, such as Bcl-2 and Bcl-3, which will avoid cell apoptosis [55][56][57]. Most notably, G6PD was found to regulate the proliferation and apoptosis of human melanoma by STAT3/STAT5 signaling pathway [58], implying the important associations of G6PD with STATs signaling pathway. Similarly, the current study revealed that G6PD siRNA significantly reduced p-STAT3 protein level, which inactivated STAT3 signaling pathway, and further triggered growth inhibition and cell apoptosis, which was achieved by decreasing the levels of cell cycle proteins cyclin D1 and CDK4 as well as cell apoptosis-related protein Bcl-2 and increasing the caspase-3 activity and Bax protein expression.…”

Section: Discussionmentioning

confidence: 98%

G6PD downregulation triggered growth inhibition and induced apoptosis by regulating STAT3 signaling pathway in esophageal squamous cell carcinoma

et al. 2015

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There is growing evidence that glucose-6-phosphate dehydrogenase (G6PD) is tightly associated with development and progression of many human tumors. However, its precise molecular mechanisms in esophageal squamous cell carcinoma (ESCC) remain unknown. In the current study, we found that G6PD messenger RNA (mRNA) and protein levels in ESCC cell lines (Eca109, EC1, and EC9706 cells) were significantly higher than that in normal esophageal epithelial cell line Het-1A (P < 0.05) and specific small interfering RNA (siRNA) against G6PD significantly reduced the levels of G6PD mRNA and protein in EC1 cells with highest G6PD levels (P < 0.05). Further investigation revealed that G6PD depletion contributed to the growth suppression in EC1 cells in vitro and EC1 cells xenografted nude mice in vivo, which was associated with the reduces of tumor weight and Ki-67 proliferation index, triggered cell cycle arrest at G0/G1 phase coupled with obvious decreases of cyclin D1 and CDK4 protein levels, and induced cell apoptosis accompanied by the increases of caspase-3 activity and Bax protein expression as well as the decrease of Bcl-2 protein expression in EC1 cells. More importantly, G6PD depletion significantly reduced the level of p-STAT3 protein but did not alter total STAT3 protein level. Taken altogether, our data presented herein suggest that G6PD may function as an important regulator in development and progression of ESCC by manipulating STAT3 signaling pathway and thus may be an underlying molecular target for therapy of the patients with ESCC.

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“…2). The pentose phosphate pathway is the first line of defense against oxidative stress in many human cells and can promote the survival of cells during neoplastic transformation and during detachment from extracellular matrix (Boada et al 2000;Debnath et al 2002;Debnath and Brugge 2005;Bensaad et al 2006;Sukhatme and Chan 2012;Hu et al 2013;Kuehne et al 2015).…”

Section: Cancer Cells Undergo Metabolic Changes To Manage Rosmentioning

confidence: 99%

Cancer, Oxidative Stress, and Metastasis

Gill

Piskounova

Morrison

2016

Cold Spring Harb Symp Quant Biol

209

146

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Reactive oxygen species (ROS) are highly reactive molecules that arise from a number of cellular sources, including oxidative metabolism in mitochondria. At low levels they can be advantageous to cells, activating signaling pathways that promote proliferation or survival. At higher levels, ROS can damage or kill cells by oxidizing proteins, lipids, and nucleic acids. It was hypothesized that antioxidants might benefit high-risk patients by reducing the rate of ROS-induced mutations and delaying cancer initiation. However, dietary supplementation with antioxidants has generally proven ineffective or detrimental in clinical trials. High ROS levels limit cancer cell survival during certain windows of cancer initiation and progression. During these periods, dietary supplementation with antioxidants may promote cancer cell survival and cancer progression. This raises the possibility that rather than treating cancer patients with antioxidants, they should be treated with pro-oxidants that exacerbate oxidative stress or block metabolic adaptations that confer oxidative stress resistance.

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Variant G6PD levels promote tumor cell proliferation or apoptosis via the STAT3/5 pathway in the human melanoma xenograft mouse model

Cited by 61 publications

References 42 publications

Changes in glucose-6-phosphate dehydrogenase expression results in altered behavior of HBV-associated liver cancer cells

Changes in glucose-6-phosphate dehydrogenase expression results in altered behavior of HBV-associated liver cancer cells

G6PD downregulation triggered growth inhibition and induced apoptosis by regulating STAT3 signaling pathway in esophageal squamous cell carcinoma

Cancer, Oxidative Stress, and Metastasis

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