Identifying the Metabolic Signatures of PPARD-Overexpressing Gastric Tumors

Pudakalakatti, Shivanand; Titus, Mark A.; Enriquez, José S.; Ramachandran, Sumankalai; Zacharias, Niki M.; Shureiqi, Imad; Liu, Yi; Yao, James C.; Zuo, Xiangsheng; Bhattacharya, Pratip K.

doi:10.3390/ijms23031645

Cited by 7 publications

(8 citation statements)

References 51 publications

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“…Oxypurinol is a metabolite with a high differential ploidy, with a differential expression ploidy (fold change) value as high as 16.45. It has the function of reducing lipid peroxide accumulation and scavenging the production of cellular superoxide radicals; some studies have found that its expression level is significantly increased in gastric tumors [ 51 , 52 ]. The increase in SOD enzyme activity in colon cancer cells after Fn evs treatment may be related to this.…”

Section: Resultsmentioning

confidence: 99%

Integrating Transcriptomics and Metabolomics to Explore the Novel Pathway of Fusobacterium nucleatum Invading Colon Cancer Cells

Yang

et al. 2023

Pathogens

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Colorectal cancer (CRC) is a malignancy with a very high incidence and mortality rate worldwide. Fusobacterium nucleatum bacteria and their metabolites play a role in inducing and promoting CRC; however, no studies on the exchange of information between Fusobacterium nucleatum extracellular vesicles (Fnevs) and CRC cells have been reported. Our research shows that Fusobacterium nucleatum ATCC25586 secretes extracellular vesicles carrying active substances from parental bacteria which are endocytosed by colon cancer cells. Moreover, Fnevs promote the proliferation, migration, and invasion of CRC cells and inhibit apoptosis; they also improve the ability of CRC cells to resist oxidative stress and SOD enzyme activity. The genes differentially expressed after transcriptome sequencing are mostly involved in the positive regulation of tumor cell proliferation. After detecting differential metabolites using liquid chromatography–tandem mass spectrometry, Fnevs were found to promote cell proliferation by regulating amino acid biosynthesis in CRC cells and metabolic pathways such as central carbon metabolism, protein digestion, and uptake in cancer. In summary, this study not only found new evidence of the synergistic effect of pathogenic bacteria and colon cancer tumor cells, but also provides a new direction for the early diagnosis and targeted treatment of colon cancer.

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Section: Resultsmentioning

confidence: 99%

Integrating Transcriptomics and Metabolomics to Explore the Novel Pathway of Fusobacterium nucleatum Invading Colon Cancer Cells

Yang

et al. 2023

Pathogens

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“…These results suggested that the gastric cancer tumor proliferation and energy fueling in PPARD-driven gastric cancer is dependent on fatty acids rather than glycolysis [66].…”

Section: Gastric Cancermentioning

confidence: 93%

“…The NMR study found significantly altered concentrations of inosine monophosphate ( p = 0.0054), adenosine monophosphate ( p = 0.009), UDP-glucose ( p = 0.0006), and oxypurinol ( p = 0.039) as PPARD mice aged from 10 weeks to 35 weeks and 55 weeks. LC–MS studies showed decreased concentrations of palmitic acid ( p = 0.0029), oleic acid ( p = 0.0007), steric acid ( p = 0.0028), and linoleic acid ( p = 0.0015) in 55 week old PPARD mice compared to 10 week old PPARD mice [ 66 ]. These results suggested that the gastric cancer tumor proliferation and energy fueling in PPARD-driven gastric cancer is dependent on fatty acids rather than glycolysis [ 66 ].…”

Section: Gastric Cancermentioning

confidence: 99%

“…LC–MS studies showed decreased concentrations of palmitic acid ( p = 0.0029), oleic acid ( p = 0.0007), steric acid ( p = 0.0028), and linoleic acid ( p = 0.0015) in 55 week old PPARD mice compared to 10 week old PPARD mice [ 66 ]. These results suggested that the gastric cancer tumor proliferation and energy fueling in PPARD-driven gastric cancer is dependent on fatty acids rather than glycolysis [ 66 ].…”

Section: Gastric Cancermentioning

confidence: 99%

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Enhancing Cancer Diagnosis with Real-Time Feedback: Tumor Metabolism through Hyperpolarized 1-13C Pyruvate MRSI

et al. 2023

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This review article discusses the potential of hyperpolarized (HP) 13C magnetic resonance spectroscopic imaging (MRSI) as a noninvasive technique for identifying altered metabolism in various cancer types. Hyperpolarization significantly improves the signal-to-noise ratio for the identification of 13C-labeled metabolites, enabling dynamic and real-time imaging of the conversion of [1-13C] pyruvate to [1-13C] lactate and/or [1-13C] alanine. The technique has shown promise in identifying upregulated glycolysis in most cancers, as compared to normal cells, and detecting successful treatment responses at an earlier stage than multiparametric MRI in breast and prostate cancer patients. The review provides a concise overview of the applications of HP [1-13C] pyruvate MRSI in various cancer systems, highlighting its potential for use in preclinical and clinical investigations, precision medicine, and long-term studies of therapeutic response. The article also discusses emerging frontiers in the field, such as combining multiple metabolic imaging techniques with HP MRSI for a more comprehensive view of cancer metabolism, and leveraging artificial intelligence to develop real-time, actionable biomarkers for early detection, assessing aggressiveness, and interrogating the early efficacy of therapies.

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“…A mouse model of PPARβ/δ overexpression in gastric progenitor cells demonstrated the development of invasive gastric tumors in aging animals. Metabolic profiling revealed that these tumors do not require glycolysis but fatty-acid oxidation for tumor progression [ 407 ]. Additionally, a high-fat diet has been shown to induce fatty-acid oxidation depending on PPARβ/δ, which is associated with intestinal stem cell activation and enhanced tumorigenesis [ 408 ], as well as colorectal metastasis formation via the activation of Nanog in colonic cancer stem cells [ 320 ].…”

Section: Ppars and Tumor Metabolismmentioning

confidence: 99%

Peroxisome Proliferator-Activated Receptors and the Hallmarks of Cancer

Wagner

2022

Cells

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Peroxisome proliferator-activated receptors (PPARs) function as nuclear transcription factors upon the binding of physiological or pharmacological ligands and heterodimerization with retinoic X receptors. Physiological ligands include fatty acids and fatty-acid-derived compounds with low specificity for the different PPAR subtypes (alpha, beta/delta, and gamma). For each of the PPAR subtypes, specific pharmacological agonists and antagonists, as well as pan-agonists, are available. In agreement with their natural ligands, PPARs are mainly focused on as targets for the treatment of metabolic syndrome and its associated complications. Nevertheless, many publications are available that implicate PPARs in malignancies. In several instances, they are controversial for very similar models. Thus, to better predict the potential use of PPAR modulators for personalized medicine in therapies against malignancies, it seems necessary and timely to review the three PPARs in relation to the didactic concept of cancer hallmark capabilities. We previously described the functions of PPAR beta/delta with respect to the cancer hallmarks and reviewed the implications of all PPARs in angiogenesis. Thus, the current review updates our knowledge on PPAR beta and the hallmarks of cancer and extends the concept to PPAR alpha and PPAR gamma.

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Identifying the Metabolic Signatures of PPARD-Overexpressing Gastric Tumors

Cited by 7 publications

References 51 publications

Integrating Transcriptomics and Metabolomics to Explore the Novel Pathway of Fusobacterium nucleatum Invading Colon Cancer Cells

Integrating Transcriptomics and Metabolomics to Explore the Novel Pathway of Fusobacterium nucleatum Invading Colon Cancer Cells

Enhancing Cancer Diagnosis with Real-Time Feedback: Tumor Metabolism through Hyperpolarized 1-13C Pyruvate MRSI

Peroxisome Proliferator-Activated Receptors and the Hallmarks of Cancer

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