Ontology highlight
ABSTRACT:
PROVIDER: PRJNA1122213 | ENA |
REPOSITORIES: ENA
Similar Datasets
Project description:ASCT2 is a major contributor to serine uptake in cancer cells
| PRJNA1122640 | ENA
Project description:The non-essential amino acid serine is a critical nutrient for cancer cells due to its diverse biosynthetic functions. While some tumors can synthesize serine de novo, others are auxotrophic and therefore reliant on serine uptake. Importantly, despite several transporters being known to be capable of transporting serine, the transporter(s) that mediate serine uptake in cancer cells are not known. Here, we characterize the amino acid transporter ASCT2 (SLC1A5) as a major contributor to serine uptake in cancer cells. ASCT2 is well-known as a glutamine transporter in cancer, and our work demonstrates that serine and glutamine compete for uptake through ASCT2. We further show that ASCT2-mediated serine uptake is essential for purine nucleotide biosynthesis and that ERα promotes serine uptake by directly activating SLC1A5 transcription. Together, our work defines an additional important role for ASCT2 as a serine transporter in cancer and evaluates ASCT2 as a potential therapeutic target.
2024-06-11 | GSE269606 | GEO
Project description:Adipocyte serine uptake curbs ROS generation and visceral adiposity
| PRJNA557596 | ENA
Project description:Cancer-associated fibroblasts (CAFs) are a major cellular component of tumor microenvironment in most solid cancers. Altered cellular metabolism is a hallmark of cancer, and much of the published literature has focused on neoplastic cell-autonomous processes for these adaptations. We demonstrate that exosomes secreted by patient-derived CAFs can strikingly reprogram the metabolic machinery following their uptake by cancer cells.
2016-04-23 | GSE80586 | GEO
Project description:Adipocyte serine uptake curbs ROS generation and visceral adiposity [Zebrafish]
| PRJNA556239 | ENA
Project description:Adipocyte serine uptake curbs ROS generation and visceral adiposity [Human]
| PRJNA557598 | ENA
Project description:DNA methylation mediated by the combined action of three DNA methyltransferases, DNMT1, DNMT3A, and DNMT3B, is essential for mammalian development and is also a major contributor to transformation. To elucidate how DNA methylation is targeted, we map the genome-wide localization of all DNMTs and methylation, and examine relationships between these markers and histone modifications and nucleosome structure. Our findings reveal a strong link between DNA methylation/DNMTs and transcribed loci and that these marks exhibit both overlapping and unique localization patterns. Comparisons with the epigenome of embryonic stem cells demonstrate that DNMT binding is associated with transformation-associated changes in methylation. Taken together, this study sheds important new light on determinants of DNA methylation and how it may become disrupted in cancer cells. Examination of different marks in undifferentiated and differentiatial NCCIT cells
2012-10-19 | E-GEOD-38937 | biostudies-arrayexpress
Project description:Mutations in cancer reprogram amino acid metabolism to drive tumor growth, but the molecular mechanisms are not well understood. Using an unbiased proteomic screen, we identified mTORC2 as a critical regulator of amino acid metabolism in cancer via phosphorylation of the cystine-glutamate antiporter xCT. mTORC2 phosphorylates serine 26 at the cytosolic N-terminus of xCT, inhibiting its activity. Genetic inhibition of mTORC2, or pharmacologic mTOR kinase inhibition, promotes glutamate secretion, cystine uptake and incorporation into glutathione linking growth factor receptor signaling with amino acid uptake and utilization. These results identify an unanticipated mechanism of amino acid metabolic reprogramming in cancer, enabling tumor cells to adapt to changing environmental conditions.
2017-06-28 | PXD006461 | Pride
Project description:Serine is a non-essential amino acid that is generated by the sequential actions of phosphoglycerate dehydrogenase (PHGDH), phosphoserine aminotransferase (PSAT1) and phosphoserine phosphatase (PSPH). Increased serine biosynthesis occurs in several cancers and supports tumor growth. In addition to serine synthesis, exogenous serine is taken up by cells and can also fuel tumor growth. Interestingly, colon cancer cells increase expression of serine biosynthesis enzymes in the absence of exogenous serine, suggesting a compensatory adaptive response to reduced availability of serine. This study explored the relative contributions of exogenous and synthesized serine to colon cancer cell growth, metabolism and response to anti-cancer therapy.
2021-11-04 | GSE144506 | GEO
Project description:Proliferating tumor cells use aerobic glycolysis to support their high metabolic demands. Paradoxically, increased glycolysis is often accompanied by expression of the lower activity PKM isoform, effectively constraining lower glycolysis. Here, we report the discovery of novel PKM activators with a unique allosteric binding mode. Characterization of how these compounds impact cancer cells revealed an unanticipated link between glucose and amino acid metabolism. PKM activation resulted in a metabolic rewiring of cancer cells manifested by a profound dependency on the non-essential amino acid serine for continued cell proliferation. Induction of serine auxotrophy by PKM activation was accompanied by reduced carbon flow into the serine biosynthetic pathway and increased expression of high affinity serine transporters. These data support the hypothesis that PKM expression confers metabolic flexibility to cancer cells that allows adaptation to nutrient stress. A549 cancer cells were treated with compound-16 for up to 24 hours in the presence and absence of serine in the media.
2012-12-20 | E-GEOD-40191 | biostudies-arrayexpress