Mitochondrial pyrimidine nucleotide carrier (PNC1) regulates mitochondrial biogenesis and the invasive phenotype of cancer cells

Favre, C.; Zhdanov, Alexander V.; Leahy, Madeline; Papkovsky, Dmitri B.; O’Connor, Rosemary

doi:10.1038/onc.2010.146

Cited by 73 publications

(71 citation statements)

References 47 publications

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“…Slc25a33-mediated uptake of UTP is important for transcription and replication of mitochondrial DNA, which again is important for mitochondrial function, i.e. increased expression of Slc25a33 enables a cancer cell to optimally produce ATP and grow while it also protects the cell from metabolic stress by preventing increased production of reactive oxygen species (Favre et al 2010). This is therefore another effect of insulin and X10 that provides cancer cells with a growth advantage.…”

Section: Endocrine-related Cancermentioning

confidence: 99%

Stimulation of MC38 tumor growth by insulin analog X10 involves the serine synthesis pathway

Hvid¹,

Fendt²,

Blouin³

et al. 2012

Endocrine-Related Cancer

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Recent evidence suggests that type II diabetes is associated with increased risk and/or aggressive behavior of several cancers, including those arising from the colon. Concerns have been raised that endogenous hyperinsulinemia and/or exogenous insulin and insulin analogs might stimulate proliferation of neoplastic cells. However, the mechanisms underlying possible growth-promoting effects of insulin and insulin analogs in cancer cells in vivo, such as changes in gene expression, are incompletely described. We observed that administration of the insulin analog X10 significantly increased tumor growth and proliferation in a murine colon cancer model (MC38 cell allografts). Insulin and X10 altered gene expression in MC38 tumors in a similar fashion, but X10 was more potent in terms of the number of genes influenced and the magnitude of changes in gene expression. Many of the affected genes were annotated to metabolism, nutrient uptake, and protein synthesis. Strikingly, expression of genes encoding enzymes in the serine synthesis pathway, recently shown to be critical for neoplastic proliferation, was increased following treatment with insulin and X10. Using stable isotopic tracers and mass spectrometry, we confirmed that insulin and X10 increased glucose contribution to serine synthesis in MC38 cells. The data demonstrate that the tumor growth-promoting effects of insulin and X10 are associated with changes in expression of genes involved in cellular energy metabolism and reveal previously unrecognized effects of insulin and X10 on serine synthesis.

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Section: Endocrine-related Cancermentioning

confidence: 99%

Stimulation of MC38 tumor growth by insulin analog X10 involves the serine synthesis pathway

Hvid¹,

Fendt²,

Blouin³

et al. 2012

Endocrine-Related Cancer

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“…The category transport contained several members of the solute carrier gene family, including SLC2A1 (glucose transporter), SLC7A3 (cationic amino acid transporter), SLC12A2 (sodium, potassium, and chloride transporter), SLC25A5 (mitochondrial carrier, adenine nucleotide translocator), SLC25A33 (mitochondrial carrier), SLC39A2 (zinc transporter), and SLC40A1 (iron transmembrane transporter). The two mitochondrial transporters, SLC25A5 and SLC25A33, have a role in cellular energy metabolism [68] and mitochondrial maintenance [69]. For the expression of the glucose transporter gene SLC2A1, regulation by conceptus prostaglandins has been shown recently in the ovine uterus [70], indicating that additional conceptus-derived factors influence the endometrial gene expression.…”

Section: Genes Not Regulated After Ifna2 Administration But On D15 Anmentioning

confidence: 99%

Comparison of the Effects of Early Pregnancy with Human Interferon, Alpha 2 (IFNA2), on Gene Expression in Bovine Endometrium1

Bauersachs¹,

Ulbrich

Reichenbach

et al. 2012

Biology of Reproduction

109

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Interferon tau (IFNT), a type I IFN similar to alpha IFNs (IFNA), is the pregnancy recognition signal produced by the ruminant conceptus. To elucidate specific effects of bovine IFNT and of other conceptus-derived factors, endometrial gene expression changes during early pregnancy were compared to gene expression changes after intrauterine application of human IFNA2. In experiment 1, endometrial tissue samples were obtained on Day (D) 12, D15, and D18 postmating from nonpregnant or pregnant heifers. In experiment 2, heifers were treated from D14 to D16 of the estrous cycle with an intrauterine device releasing IFNA2 or, as controls, placebo lipid extrudates or PBS only. Endometrial biopsies were performed after flushing the uterus. All samples from both experiments were analyzed with an Affymetrix Bovine Genome Array. Experiment 1 revealed differential gene expression between pregnant and nonpregnant endometria on D15 and D18. In experiment 2, IFNA2 treatment resulted in differential gene expression in the bovine endometrium. Comparison of the data sets from both studies identified genes that were differentially expressed in response to IFNA2 but not in response to pregnancy on D15 or D18. In addition, genes were found that were differentially expressed during pregnancy but not after IFNA2 treatment. In experiment 3, spatiotemporal alterations in expression of selected genes were determined in uteri from nonpregnant and early pregnant heifers using in situ hybridization. The overall findings of this study suggest differential effects of bovine IFNT compared to human IFNA2 and that some pregnancy-specific changes in the endometrium are elicited by conceptus-derived factors other than IFNT.endometrium, hormone action, pregnancy, reproductive immunology, uterus

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“…Additionally, we have recently shown that miR-200c, an miRNA only modestly expressed in the heart, is increased in ZO rat heart, and this increase in miR-200c may serve as a compensatory mechanism to downregulate excessive activation of the nutrient sensor kinase S6K1 [176] . The miR-200 family is implicated in the epithelial-to-mesenchymal transition (EMT) that is accompanied by mitochondrial biogenesis and involved in organ fibrosis and carcinoma progression [177][178][179][180][181][182][183][184] . It was reported that miR-200 is down-regulated in EMT, and that overexpression of miR-200b can attenuate EMT [179] .…”

Section: Mirna Regulation Of Apoptosismentioning

confidence: 99%

Mitochondria and Oxidative Stress in the Cardiorenal Metabolic Syndrome

et al. 2012

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Mitochondria play a fundamental role in the maintenance of normal structure, function, and survival of tissues. There is considerable evidence for mitochondrial dysfunction in association with metabolic diseases including insulin resistance, obesity, diabetes, and the cardiorenal metabolic syndrome. The phenomenon of reactive oxygen species (ROS)-induced ROS release through interactions between cytosolic and mitochondrial oxidative stress contributes to a vicious cycle of enhanced oxidative stress and mitochondrial dysfunction. Activation of the cytosolic and mitochondrial NADPH oxidase system, impairment of the mitochondrial electron transport, activation of p66shc pathway-targeting mitochondria, endoplasmic reticular stress, and activation of the mammalian target of the rapamycin-S6 kinase pathway underlie dysregulation of mitochondrial dynamics and promote mitochondrial oxidative stress. These processes are further modulated by acetyltransferases including sirtuin 1 and sirtuin 3, the former regulating nuclear acetylation and the latter regulating mitochondrial acetylation. The regulation of mitochondrial functions by microRNAs forms an additional layer of molecular control of mitochondrial oxidative stress. Alcohol further exacerbates mitochondrial oxidative stress induced by overnutrition and promotes the development of metabolic diseases.

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Mitochondrial pyrimidine nucleotide carrier (PNC1) regulates mitochondrial biogenesis and the invasive phenotype of cancer cells

Cited by 73 publications

References 47 publications

Stimulation of MC38 tumor growth by insulin analog X10 involves the serine synthesis pathway

Stimulation of MC38 tumor growth by insulin analog X10 involves the serine synthesis pathway

Comparison of the Effects of Early Pregnancy with Human Interferon, Alpha 2 (IFNA2), on Gene Expression in Bovine Endometrium1

Mitochondria and Oxidative Stress in the Cardiorenal Metabolic Syndrome

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