Attenuation of LDHA expression in cancer cells leads to redox-dependent alterations in cytoskeletal structure and cell migration

Arseneault, Robert; Chien, Andrew; Newington, Jordan T.; Rappon, Tim; Harris, Richard; Cumming, Robert

doi:10.1016/j.canlet.2013.03.034

Cited by 69 publications

(64 citation statements)

References 35 publications

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“…At the molecular level, these effects were related to decreased Akt activation and cyclin D1 expression, increased cleavage of PARP and caspases [84] and downregulation of Oct4 [88]. An additional common finding observed in cancer cells with LDH-A knockdown is an elevated mitochondrial ROS production [86,87]; besides facilitating cell death, the resulting oxidative stress condition was found to affect cytoskeletal structure, explaining the migration defects observed in treated cells [87]. Inhibition of LDH-A was also found to be a way to overcome the acquired resistance of breast cancer cells to taxol [89] and trastuzumab [90], two chemotherapeutics widely used in the treatment of this tumor form.…”

Section: Ldh-a and Ldh-b: Which Is The Most Appropriate Anticancer Target?mentioning

confidence: 99%

“…LDH-A expression is constantly up-regulated in tumors and was found to correlate with tumor size and prognosis [49][50][51]54]. In several tumor models, silencing LDH-A expression by siRNA or shRNA was found to inhibit cell growth, migration and in vivo tumorigenesis [83][84][85][86][87][88]. At the molecular level, these effects were related to decreased Akt activation and cyclin D1 expression, increased cleavage of PARP and caspases [84] and downregulation of Oct4 [88].…”

Section: Ldh-a and Ldh-b: Which Is The Most Appropriate Anticancer Target?mentioning

confidence: 99%

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Inhibition of Lactate Dehydrogenase Activity as an Approach to Cancer Therapy

et al. 2014

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In the attempt of developing innovative anticancer treatments, growing interest has recently focused on the peculiar metabolic properties of cancer cells. In this context, LDH, which converts pyruvate to lactate at the end of glycolysis, is emerging as one of the most interesting molecular targets for the development of new inhibitors. In fact, because LDH activity is not needed for pyruvate metabolism through the TCA cycle, inhibitors of this enzyme should spare glucose metabolism of normal non-proliferating cells, which usually completely degrade the glucose molecule to CO2. This review is aimed at summarizing the available data on LDH biology in normal and neoplastic cells, which support the anticancer therapeutic approach based on LDH inhibition. These data encouraged pharmaceutical industries and academic institutions in the search of small-molecule inhibitors and promising candidates have recently been identified. The availability of inhibitors with drug-like properties will allow the evaluation in the near future of the real potential of LDH inhibition in anticancer treatment, also making the identification of the most responsive neoplastic conditions possible.

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Section: Ldh-a and Ldh-b: Which Is The Most Appropriate Anticancer Target?mentioning

confidence: 99%

Section: Ldh-a and Ldh-b: Which Is The Most Appropriate Anticancer Target?mentioning

confidence: 99%

Inhibition of Lactate Dehydrogenase Activity as an Approach to Cancer Therapy

et al. 2014

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“…Protein encoded by this gene catalyzes the conversion of L-lactate and NAD to pyruvate and NADH in the final step of anaerobic glycolysis. Importantly, LDHA is upregulated in tumors and promotes cellular proliferation and tumorigenesis [30–32]. The co-expression of NR_028500 and LDHA implies that NR_028500 may be involved in the anaerobic glycolysis of tumor cells.…”

Section: Discussionmentioning

confidence: 99%

Identification of long noncoding RNAs for the detection of early stage lung squamous cell carcinoma by microarray analysis

et al. 2017

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The aberrant expressions of long noncoding RNAs have been reported in numerous cancers, which have facilitated the cancer diagnosis. However, the expression profile of lncRNAs in early stage lung squamous cell carcinoma has not been well discussed. The present study aimed to examine the expression profile of lncRNAs in early stage lung squamous cell carcinoma and identify lncRNA biomarkers for diagnosis. Through high-throughput lncRNA microarray, we screened thousands of aberrantly expressed lncRNAs and mRNAs in early stage lung squamous cell carcinoma tissues compared to their corresponding adjacent nontumorous tissues. Bioinformatics analyses were used to investigate the functions of aberrantly expressed mRNAs and their associated lncRNAs. After that, in order to identify lncRNA biomarkers for early detection, candidate lncRNA biomarkers were selected based on our established filtering pipeline and validated by real-time quantitative polymerase chain reaction on a total of 63 pairs of tumor samples. Five lncRNAs were finally identified which were able to distinguish early stage tumor and normal samples with high sensitivity (92%) and specificity (83%). These results imply that lncRNAs may be powerful biomarker for early diagnosis.

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“…Importantly, LDHA is often upregulated in oncogenic environments and cancer cells serving a protective role by reducing ROS, subsequent DNA damage, and apoptosis. This encourages oncogenic pathway persistence, cancer cell growth and proliferation [6,7].…”

Section: Discussionmentioning

confidence: 99%

“…Additionally, activating and synergistically enhancing the function of IL-1β, oxidative stress induced ROS also upregulates lactose dehydrogenase (LDH). LDH is an oxidoreductase that interconverts pyruvate and lactate with concomitant interconversion of NADH and NAD +, and is an accepted biomarker of oxidative stress [6,7].…”

mentioning

confidence: 99%

Exhaled Biomarkers of Oxidative Stress and Inflammation in Hookah Smokers: A Public Health Concern

Alnashwan

Hakamy

Gongol

et al. 2015

GJCT

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Current public policy does not reflect health risk awareness associated with hookah smoking. Although, cigaretteÃ‚Â smoking has gained considerable attention accompanied by public restrictions, hookah smoking continues toÃ‚Â increase as an unrestricted, socially acceptable means of recreation. This study identified novel biomarkersÃ‚Â altered by hookah smoking compared to cigarette smoking using exhaled breath condensate collected fromÃ‚Â nonsmokers, hookah smokers and cigarette smokers pre and post smoking. Both cigarette and hookah smokershad higher levels of inflammatory mediators suggestive of inflammasome activation as well as altered expressionÃ‚Â of miR-217 and miR-17, which are known to regulate inflammasome activation and promote oncogenesis. Toassess current public knowledge of risk factors and behaviors associated with hookah smoking, and if knowledgeÃ‚Â of hookah dangers would influence smoking behaviors, the experimental data were integrated into a surveyÃ‚Â emphasizing cancer risk associated with hookah smoking. Survey results indicated that 70% of study participantsÃ‚Â were encouraged to abstain from hookah smoking after gaining knowledge of cancer risk associated with hookah.Ã‚Â The identification of behaviors associated with hookah smoking and novel biomarkers of health risk may influenceits public health regulation and facilitate community health education.

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Attenuation of LDHA expression in cancer cells leads to redox-dependent alterations in cytoskeletal structure and cell migration

Cited by 69 publications

References 35 publications

Inhibition of Lactate Dehydrogenase Activity as an Approach to Cancer Therapy

Inhibition of Lactate Dehydrogenase Activity as an Approach to Cancer Therapy

Identification of long noncoding RNAs for the detection of early stage lung squamous cell carcinoma by microarray analysis

Exhaled Biomarkers of Oxidative Stress and Inflammation in Hookah Smokers: A Public Health Concern

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