Expression of pyruvate carboxylase in cultured human astrocytoma, glioblastoma and neuroblastoma cells

Gondáš, Eduard; Trančiková, Alžbeta; Majerčíková, Zuzana; Pokusa, Michal; Baranovičová, Eva; Bystrický, Peter; Dobrota, Dušan; Murín, Radovan

doi:10.4149/gpb_2021003

Cited by 6 publications

(8 citation statements)

References 35 publications

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“…F14512, a topoisomerase II inhibitor containing the spermine fraction, was found to have significant and long-lasting antitumor effects on NB and to have synergistic effects with cisplatin and carboplatin ( 60 ). The presence of pyruvate carboxylase (PC), which converts pyruvate to oxaloacetate, has now been demonstrated in NB ( 61 ). In addition, it is believed that cancer cells can use Lactate dehydrogenase(LDH) to reduce pyruvate to lactate in order to bypass oxidative phosphorylation ( 62 ), and the increased lactate level can enhance tumor angiogenesis and facilitate tumor growth ( 63 , 64 ), but we found that the level of lactate metabolism in NEs is lower than that in T cells.…”

Section: Discussionmentioning

confidence: 99%

Single-cell transcriptome sequencing reveals tumor heterogeneity in family neuroblastoma

Zhang,

Ma,

Liu

et al. 2023

Front. Immunol.

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Neuroblastoma(NB) is the most common extracranial solid tumor in childhood, and it is now believed that some patients with NB have an underlying genetic susceptibility, which may be one of the reasons for the multiplicity of NB patients within a family line. Even within the same family, the samples show great variation and can present as ganglioneuroblastoma or even benign ganglioneuroma. The genomics of NB is still unclear and more in-depth studies are needed to reveal its key components. We first performed single-cell RNA sequencing(sc-RNAseq) analysis on clinical specimens of two family neuroblastoma(FNB) and four sporadic NB cases. A complete transcriptional profile of FNB was constructed from 18,394 cells from FNB, and we found that SDHD may be genetically associated with FNB and identified a prognostic related CAF subtype in FNB: Fib-4. Single-cell flux estimation analysis (scFEA) results showed that malignant cells were associated with arginine spermine, oxaloacetate and hypoxanthine, and that malignant cells metabolize lactate at lower levels than T cells. Our study provides new resources and ideas for the development of the genomics of family NB, and the mechanisms of cell-to-cell interactions and communication and the metabolic landscape will provide new therapeutic targets.

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Section: Discussionmentioning

confidence: 99%

Single-cell transcriptome sequencing reveals tumor heterogeneity in family neuroblastoma

Zhang,

Ma,

Liu

et al. 2023

Front. Immunol.

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“…The primary antibodies applied in the study were initially derived against the bovine orthologue of PC (28). Due to a high degree of homology in primary sequences between bovine and human PC orthologues (20,29) and capability to recognize only PC among several types of protein lysates derived from different human cells and tissues (12), the used antibodies can be considered suitable also for the dot-blot analysis performed on human prostate tumor lysates.…”

Section: Discussionmentioning

confidence: 99%

“…Several study models had been exploited to study and obtain the results dealing with the altered expression of genes during carcinogenesis and their function in cancer metabolism. Indeed, PC expression and function were studied on several types of cultured cancer cell lines of human origin and animal models (5,5,(12)(13)(14)(15)(16)(17)(18)(19)(20). However, the complexity in the regulation of PC expression might be limiting with respect to the translational aspect of those results.…”

Section: Discussionmentioning

confidence: 99%

“…Only a few reactions possess the anaplerotic role in cellular metabolism. In addition to glutamine catabolism, which is considered a prominent anaplerotic process in cancer cells (8)(9)(10)(11), pyruvate carboxylation has been recognized as being necessary for sustaining the growth and viability of several types of cancer cells even in the presence of glutamine (5,5,(12)(13)(14)(15)(16)(17)(18)(19)(20).…”

Section: Introductionmentioning

confidence: 99%

“…The in vitro experiments on several types of cultured human cancer cells revealed that the anaplerotic process profoundly impacts their cellular metabolism, biosynthetic capacity, growth, and viability (12,13,15,(17)(18)(19)(23)(24)(25)(26). The importance of the anaplerotic process for supporting the growth and survival of cancer cells might be exploited to develop new diagnostic tools and therapeutic approaches.…”

Section: Introductionmentioning

confidence: 99%

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The ubiquitous expression of pyruvate carboxylase among human prostate tumors

Gondáš¹,

Híveš²,

Kliment³

et al. 2022

BLL

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Pyruvate carboxylase (PC) is a mitochondrial enzyme catalyzing the ATP-dependent reaction of pyruvate prolongation with bicarbonate ion to oxaloacetate. The synthesis of oxaloacetate by PC, an intermediate of the Krebs cycle, is recently recognized as a signifi cant anaplerotic reaction that supports the biosynthetic capability, growth, aggressiveness, and even viability of several cancer cell types. PC expression was confi rmed in several types of cancer cells and tumors. To evaluate the possibility that prostate tumor-forming cells are also exploiting the anaplerotic role of PC, we applied immunoblotting analysis to estimate its presence. Our results revealed that PC is present among the lysate proteins derived from prostate cancer and benign prostatic hyperplasia samples. The expression of PC in cells of prostate tumors and benign prostatic hyperplasia supposes that PC could facilitate the formation of oxaloacetate in situ and enhance the autonomy of their biosynthetic metabolism from the availability of extracellular substrates by increasing the cellular anaplerotic capability (Tab. 1, Fig. 1, Ref. 30).

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Immunodetection of Pyruvate Carboxylase Expression in Human Astrocytomas, Glioblastomas, Oligodendrogliomas, and Meningiomas

et al. 2023

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Pyruvate carboxylase (PC) is an enzyme catalyzing the carboxylation of pyruvate to oxaloacetate. The enzymatic generation of oxaloacetate, an intermediate of the Krebs cycle, could provide the cancer cells with the additional anaplerotic capacity and promote their anabolic metabolism. Recent studies revealed that several types of cancer cells express PC. The gained anaplerotic capability of cells mediated by PC correlates with their expedited growth, higher aggressiveness, and increased metastatic potential. By immunohistochemical staining and immunoblotting analysis, we investigated PC expression among samples of different types of human brain tumors. Our results show that PC is expressed by the cells in glioblastoma, astrocytoma, oligodendroglioma, and meningioma tumors. The presence of PC in these tumors suppose that PC could support the anabolic metabolism of their cellular constituents by its anaplerotic capability.

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Expression of pyruvate carboxylase in cultured human astrocytoma, glioblastoma and neuroblastoma cells

Cited by 6 publications

References 35 publications

Single-cell transcriptome sequencing reveals tumor heterogeneity in family neuroblastoma

Single-cell transcriptome sequencing reveals tumor heterogeneity in family neuroblastoma

The ubiquitous expression of pyruvate carboxylase among human prostate tumors

Immunodetection of Pyruvate Carboxylase Expression in Human Astrocytomas, Glioblastomas, Oligodendrogliomas, and Meningiomas

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