The NDPK/NME superfamily: state of the art

2 SummaryReprogrammed metabolism and cell cycle dysregulation are two cancer hallmarks. p16 is a cell cycle inhibitor and tumor suppressor that is upregulated during oncogeneinduced senescence (OIS). Loss of p16 allows for uninhibited cell cycle progression, bypass of OIS, and tumorigenesis. Whether p16 loss affects pro-tumorigenic metabolism is unclear. We report that suppression of p16 plays a central role in

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“…5A). NME1 is a known metastasis suppressor (Boissan et al, 2018); therefore, we focused on RPIA (Fig. 5B).…”

Section: Atr Activates Mtorc1 To Increase Nucleotide Synthesismentioning

confidence: 99%

Suppression of p16 induces mTORC1-mediated nucleotide metabolic reprogramming

Buj

Chen

Dahl

et al. 2018

Preprint

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“…For example, the Nme1 and Nme2 genes are known to be part of the Nm23 gene family, and have been shown to be responsible for the majority of NDP kinase activity in mammals (Postel et al, 2009) along with other cellular processes (Boissan et al, 2018). Nme1 and Nme2 can be co-transcribed, forming a fusion protein (Akiva et al, 2006;Prakash et al, 2010).…”

Section: Mouse Embryo Datamentioning

confidence: 99%

Compression of quantification uncertainty for scRNA-seq counts

Buren

Sarkar

Srivastava

et al. 2020

Preprint

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AbstractMotivationQuantification estimates of gene expression from single-cell RNA-seq (scRNA-seq) data have inherent uncertainty due to reads that map to multiple genes. Many existing scRNA-seq quantification pipelines ignore multi-mapping reads and therefore underestimate expected read counts for many genes. alevin accounts for multi-mapping reads and allows for the generation of “inferential replicates”, which reflect quantification uncertainty. Previous methods have shown improved performance when incorporating these replicates into statistical analyses, but storage and use of these replicates increases computation time and memory requirements.ResultsWe demonstrate that storing only the mean and variance from a set of inferential replicates (“compression”) is sufficient to capture gene-level quantification uncertainty. Using these values, we generate “pseudo-inferential” replicates from a negative binomial distribution and propose a general procedure for incorporating these replicates into a proposed statistical testing framework. We show reduced false positives when applying this procedure to trajectory-based differential expression analyses. We additionally extend the Swish method to incorporate pseudo-inferential replicates and demonstrate improvements in computation time and memory consumption without any loss in performance. Lastly, we show that the removal of multi-mapping reads can result in significant underestimation of counts for functionally important genes in a real dataset.Availability and implementationmakeInfReps and splitSwish are implemented in the development branch of the R/Bioconductor fishpond package available at http://bioconductor.org/packages/devel/bioc/html/fishpond.html. Sample code to calculate the uncertainty-aware p-values can be found on GitHub at https://github.com/skvanburen/scUncertaintyPaperCode.Contactmichaelisaiahlove@gmail.com

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“…Increased NME1 expression in primary breast tumors is also associated with worse prognosis in breast cancer patients (Extended Data Fig 5a). NME1 catalyzes the transfer of a phosphate from nucleoside triphosphates (NTPs) to nucleoside diphosphates (NDPs), primarily from ATP to GDP to produce GTP for use in G protein signalling 37 .…”

Section: Nme1 Promotes Lung Metastasis From Patient Tumor Cellsmentioning

confidence: 99%

Patient-derived xenograft culture-transplant system for investigation of human breast cancer metastasis

Ma¹,

Hernandez²,

Lefebvre³

et al. 2020

Preprint

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Metastatic disease carries a poor prognosis and its study is limited by the availability of authentic experimental models. Here, we present a 3D tumor sphere culture-transplant system that facilitates expansion and modulation of patient-derived xenograft (PDX) cells for use in functional experimental metastasis assays. RNA sequencing shows PDX tumor spheres maintain fundamental properties of native tumor cells. In vivo transplantation studies demonstrate cultured cells yield robust spontaneous and experimental metastasis following orthotopic and intravenous or intracardiac delivery, respectively. Pharmacologic inhibition of previously reported metastasis-promoting pathways also inhibits metastasis of PDX cells after culture, validating our approach. Finally, we used our culture-transplant system to demonstrate a new role of the metabolic enzyme NME1 in promoting breast cancer metastasis. Thus, we present a novel method for authentic propagation, engineering and transplantation of PDX models for functional studies of metastasis using bona fide patient tumor cells.

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The NDPK/NME superfamily: state of the art

Cited by 74 publications

References 134 publications

Suppression of p16 induces mTORC1-mediated nucleotide metabolic reprogramming

Suppression of p16 induces mTORC1-mediated nucleotide metabolic reprogramming

Compression of quantification uncertainty for scRNA-seq counts

Patient-derived xenograft culture-transplant system for investigation of human breast cancer metastasis

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