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Exogenous and Endogenous Sources of Serine Contribute to Colon Cancer Metabolism and Growth

ABSTRACT: Exogenous and Endogenous Sources of Serine Contribute to Colon Cancer Metabolism and Growth

PROVIDER: PRJNA603833 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR10987339_1.fastq.gz	Fastqsanger.gz
	SRR10987339_2.fastq.gz	Fastqsanger.gz
	SRR10987340_1.fastq.gz	Fastqsanger.gz
	SRR10987340_2.fastq.gz	Fastqsanger.gz
	SRR10987341_1.fastq.gz	Fastqsanger.gz

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Exogenous and Endogenous Sources of Serine Contribute to Colon Cancer Metabolism and Growth

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

Exogenous and endogenous serine modulate polarization of tumor-associated macrophages to influence development of nasopharyngeal carcinoma

Project description:To investigate the global gene expression pattern in response to removal of exogenous serine/glycine from the medium, RNA-seq was performed using C666-1 cells cultured in CM or -SG medium for 24 h. The volcano plot exhibited 60 up-regulated and 123 down-regulated genes in C666-1 cells subjected to exogenous serine/glycine deprivation.

2024-04-09 | GSE263382 | GEO

Exogenous and endogenous serine modulate polarization of tumor-associated macrophages to influence development of nasopharyngeal carcinoma

Project description:Exogenous and endogenous serine modulate polarization of tumor-associated macrophages to influence development of nasopharyngeal carcinoma

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Exogenous and Endogenous Sources of Serine Contribute to Colon Cancer Metabolism, Growth, and Resistance to 5-Fluorouracil.

Project description:Serine is a nonessential amino acid 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, cancer cells can harness exogenous serine to enhance their metabolism and proliferation. Here we tested the relative contributions of exogenous and endogenous sources of serine on the biology of colorectal cancer. In murine tumors, Apc status was identified as a determinant of the expression of genes controlling serine synthesis. In patient samples, PSAT1 was overexpressed in both colorectal adenomas and adenocarcinomas. Combining genetic deletion of PSAT1 with exogenous serine deprivation maximally suppressed the proliferation of colorectal cancer cells and induced profound metabolic defects including diminished nucleotide production. Inhibition of serine synthesis enhanced the transcriptional changes following exogenous serine removal as well as alterations associated with DNA damage. Both loss of PSAT1 and removal of serine from the diet were necessary to suppress colorectal cancer xenograft growth and enhance the antitumor activity of 5-fluorouracil (5-FU). Restricting endogenous and exogenous serine in vitro augmented 5-FU-induced cell death, DNA damage, and metabolic perturbations, likely accounting for the observed antitumor effect. Collectively, our results suggest that both endogenous and exogenous sources of serine contribute to colorectal cancer growth and resistance to 5-FU. SIGNIFICANCE: These findings provide insights into the metabolic requirements of colorectal cancer and reveal a novel approach for its treatment. GRAPHICAL ABSTRACT: http://cancerres.aacrjournals.org/content/canres/81/9/2275/F1.large.jpg.

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Bioinformatic analysis of endogenous and exogenous small RNAs on lipoproteins

Project description:Bioinformatic analysis of endogenous and exogenous small RNAs on lipoproteins

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HLA-DP(84Gly) constitutively presents endogenous peptides generated by the class I antigen processing pathway

Project description:Classical antigen processing/presentation mechanisms lead to the presentation of antigenic peptides derived from endogenous and exogenous sources for MHC class I and class II molecules, respectively. We show here that, unlike other class II, prevalent HLA-DP molecules whose chains encode Gly84 (DP84Gly) constitutively present endogenous peptides.

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SETDB1 Represses Endogenous and Exogenous Retroviruses in B Lymphocytes [RNA-Seq]

Project description:Genome stability relies on epigenetic mechanisms that enforce repression of endogenous retroviruses (ERVs). Current evidence suggests that distinct chromatin-based mechanisms repress ERVs in cells of embryonic origin (histone methylation-dominant) versus more differentiated cells (DNA methylation-dominant). However, the latter aspect of this model has not been tested. Remarkably, and in contrast to the prevailing model, we find that repressive histone methylation catalyzed by the enzyme SETDB1 is critical for suppression of specific ERV families and exogenous retroviruses in committed B-lineage cells from adult mice. The profile of ERV activation in SETDB1-deficient B cells is distinct from that observed in corresponding embryonic tissues, despite the loss of repressive chromatin modifications at all ERVs. We provide evidence that, upon loss of SETDB1, ERVs are activated in a lineage-specific manner depending on the set of transcription factors available to target proviral regulatory elements. These findings have important implications for genome stability in somatic cells, as well as the interface between epigenetic repression and viral latency. Expression profiling and bisulfite PCR sequencing in Setdb1 C/C and Setdb1 D/D pro-B cells

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Serine Metabolism Orchestrates Macrophage Polarization by Regulating the IGF1–p38 Axis

Project description:Here we show that suppressing the serine biosynthesis pathway, either by inhibiting the activity of the key enzyme phosphoglycerate dehydrogenase or by exogenous serine and glycine restriction, robustly enhances polarization of interferon-g-activated macrophages (M(IFN-g)) but suppresses that of interleukin-4-activated macrophages (M(IL-4)) both in vitro and in vivo.To further explore its mechanism, we used high-throughput sequencing technology (RNA-seq) to assess gene expression in serine-deficiency or not BMDMs

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SETDB1 Represses Endogenous and Exogenous Retroviruses in B Lymphocytes [array]

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SETDB1 Represses Endogenous and Exogenous Retroviruses in B Lymphocytes [RNA-Seq]

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