The progression from a lower to a higher invasive stage of bladder cancer is associated with severe alterations in glucose and pyruvate metabolism

Conde, Vanessa R.; Oliveira, Pedro F.; Nunes, Ana R.; Rocha, Cátia S.; Ramalhosa, Elsa; Pereira, José Alberto; Alves, Marco G.; Silva, Branca M.

doi:10.1016/j.yexcr.2015.04.007

Cited by 78 publications

(75 citation statements)

References 47 publications

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“…44,45 The metabolomics profile of NSD3s + and Pdp3 + is similar; however, not identical, indicating that each protein acts by regulating a common core of metabolic pathways in addition to a handful of other proteinspecific reactions. Consistent to our findings, these metabolic alterations have been frequently found in several types of tumors, including those in which NSD3s overexpression is reported 33,38,40,41,[52][53][54][55][56][57] . This effect is a characteristic of the metabolic alterations found in tumorigenesis, in which tumor cells adapt their pathways to the production of macromolecules necessary to sustain growth and survival.…”

Section: Discussionsupporting

confidence: 90%

¹H NMR metabolomics reveals increased glutaminolysis upon overexpression of NSD3s or Pdp3 in Saccharomyces cerevisiae

Rona

Almeida

Santos

et al. 2018

J of Cellular Biochemistry

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NSD3s, the proline‐tryptophan‐tryptophan‐proline (PWWP) domain‐containing, short isoform of the human oncoprotein NSD3, displays high transforming properties. Overexpression of human NSD3s or the yeast protein Pdp3 in Saccharomyces cerevisiae induces similar metabolic changes, including increased growth rate and sensitivity to oxidative stress, accompanied by decreased oxygen consumption. Here, we set out to elucidate the biochemical pathways leading to the observed metabolic phenotype by analyzing the alterations in yeast metabolome in response to NSD3s or Pdp3 overexpression using 1H nuclear magnetic resonance (NMR) metabolomics. We observed an increase in aspartate and alanine, together with a decrease in arginine levels, on overexpression of NSD3s or Pdp3, suggesting an increase in the rate of glutaminolysis. In addition, certain metabolites, including glutamate, valine, and phosphocholine were either NSD3s or Pdp3 specific, indicating that additional metabolic pathways are adapted in a protein‐dependent manner. The observation that certain metabolic pathways are differentially regulated by NSD3s and Pdp3 suggests that, despite the structural similarity between their PWWP domains, the two proteins act by unique mechanisms and may recruit different downstream signaling complexes. This study establishes for the first time a functional link between the human oncoprotein NSD3s and cancer metabolic reprogramming.

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Section: Discussionsupporting

confidence: 90%

¹H NMR metabolomics reveals increased glutaminolysis upon overexpression of NSD3s or Pdp3 in Saccharomyces cerevisiae

Rona

Almeida

Santos

et al. 2018

J of Cellular Biochemistry

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“…FFAs bind PPAR γ and other PPAR isoforms and activate transcriptional activity. Other dysregulated metabolic pathways, including those that involve glycolysis [78], can cause a metabolic switch regulated by oncogenes and tumor suppressor genes to favor tumor growth and play a role in bladder carcinogenesis. Together, these observations are consistent with evidence showing lower expression levels of A-FABP and higher expression levels of FAS in more invasive forms of bladder cancer.…”

Section: An Independent Microenvironment Through Pparγmentioning

confidence: 99%

Deciphering the Roles of Thiazolidinediones and PPARγin Bladder Cancer

et al. 2017

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The use of thiazolidinedione (TZD) therapy in type II diabetic patients has proven useful in the lowering of blood glucose levels. However, recent investigations have shown that there may be potential health concerns associated, including the risk of developing bladder cancer as well as complications in the cardiovasculature. TZDs are ligands for the nuclear receptor PPARγ, and activation causes lipid uptake and insulin sensitization, both of which are critical processes for diabetic patients whose bodies are unable to utilize insulin effectively. Several studies have shown that PPARγ/TZDs decrease IGF-1 levels and, thus, reduce cancer growth in carcinomas such as the pancreas, colon, liver, and prostate. However, other studies have shed light on the potential of the receptor as a biomarker for uroepithelial carcinomas, particularly due to its stimulatory effect on migration of bladder cancer cells. Furthermore, PPARγ may provide the tumor-promoting microenvironment by de novo synthesis of nutrients that are needed for bladder cancer development. In this review, we closely examine the TZD class of drugs and their effects on PPARγ in patient studies along with additional molecular factors that are positive modulators, such as protein phosphatase 5 (PP5), which may have considerable implications for bladder cancer therapy.

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“…Acylphosphatase 2 can hydrolyze the phosphoenzyme intermediate of different membrane pumps, particularly the Ca 2+ /Mg 2+ ‐ATPase from the sarcoplasmic reticulum of skeletal muscle (Nassi, Nediani, Liguri, Taddei, & Ramponi, ). Studies have revealed that ACYP2 plays a crucial role in pyruvate metabolism whose activation is an important factor for malignant transformation (Conde et al, ; Szlosarek, Lee, & Pollard, ; Won et al, ). Furthermore, ACYP2 has been confirmed as a telomere length‐related gene (Codd et al, ).…”

Section: Discussionmentioning

confidence: 99%

Assessment of the association between ACYP2 and laryngeal squamous cell carcinoma risk in Chinese males

Zhao

Niu

Xie

et al. 2019

Molec Gen & Gen Med

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Background Laryngeal squamous cell carcinoma (LSCC) is one of the most prevalent malignant neoplasms of the upper respiratory tract. Studies have confirmed that an unstable chromosome constitution promotes the progress of laryngeal tumorigenesis, and ACYP2 has been confirmed as a telomere length‐related gene. However, to date, the association between ACYP2 polymorphisms and LSCC susceptibility has not been investigated. Methods We performed this study to explore the effect of 11 single‐nucleotide polymorphisms (SNPs) in ACYP2 on LSCC susceptibility in Chinese Han males. Unconditional logistic regression analysis adjusted for age was used to calculate the odds ratios and 95% confidence intervals. Results Based on allele and genotype models, our results showed that rs1682111 variant was significantly associated with a decreased LSCC susceptibility ( p < 0.05). On the contrary, polymorphisms of rs10439478, rs11125529, rs12615793, rs843711, rs11896604, and rs17045754 were significantly associated with an increased LSCC risk ( p < 0.05). The results of haplotype analysis indicated that haplotypes “TTCTCG” and “TTCTAA” in block 1 and “TG” in block 2 showed a risk factor for the development of LCSS ( p = 0.009, p < 0.001, and p = 0.001, respectively). The results of Genotype‐Tissue Expression analysis indicate that these significant SNPs were known to be associated with ACYP2 expression. Conclusion Our data demonstrated that ACYP2 polymorphisms may exert effects on LSCC susceptibility in Chinese Han males.

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The progression from a lower to a higher invasive stage of bladder cancer is associated with severe alterations in glucose and pyruvate metabolism

Cited by 78 publications

References 47 publications

¹H NMR metabolomics reveals increased glutaminolysis upon overexpression of NSD3s or Pdp3 in Saccharomyces cerevisiae

¹H NMR metabolomics reveals increased glutaminolysis upon overexpression of NSD3s or Pdp3 in Saccharomyces cerevisiae

Deciphering the Roles of Thiazolidinediones and PPARγin Bladder Cancer

Assessment of the association between ACYP2 and laryngeal squamous cell carcinoma risk in Chinese males

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The progression from a lower to a higher invasive stage of bladder cancer is associated with severe alterations in glucose and pyruvate metabolism

Cited by 78 publications

References 47 publications

1H NMR metabolomics reveals increased glutaminolysis upon overexpression of NSD3s or Pdp3 in Saccharomyces cerevisiae

1H NMR metabolomics reveals increased glutaminolysis upon overexpression of NSD3s or Pdp3 in Saccharomyces cerevisiae

Deciphering the Roles of Thiazolidinediones and PPARγin Bladder Cancer

Assessment of the association between ACYP2 and laryngeal squamous cell carcinoma risk in Chinese males

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¹H NMR metabolomics reveals increased glutaminolysis upon overexpression of NSD3s or Pdp3 in Saccharomyces cerevisiae

¹H NMR metabolomics reveals increased glutaminolysis upon overexpression of NSD3s or Pdp3 in Saccharomyces cerevisiae