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Thymidylate synthase maintains the de-differentiated state of triple negative breast cancers

ABSTRACT: Thymidylate synthase maintains the de-differentiated state of triple negative breast cancers

PROVIDER: PRJNA506989 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR8244640.fastq.gz	Fastqsanger.gz
	SRR8244641.fastq.gz	Fastqsanger.gz
	SRR8244642.fastq.gz	Fastqsanger.gz
	SRR8244643.fastq.gz	Fastqsanger.gz

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Thymidylate synthase maintains the de-differentiated state of triple negative breast cancers

Project description:Cancer cells frequently boost nucleotide metabolism (NM) to support their increased proliferation, but the consequences of elevated NM on tumor de-differentiation are mostly unexplored. Here, we identified a role for thymidylate synthase (TS), a NM enzyme and established drug target, in cancer cell de-differentiation and investigated its clinical significance in breast cancer (BC). In vitro, TS knockdown increased the population of CD24+ differentiated cells, and attenuated migration and sphere-formation. RNA-seq profiling indicated a repression of epithelial-to-mesenchymal transition (EMT) signature genes upon TS knockdown, and TS-deficient cells showed an increased ability to invade and metastasize in vivo, consistent with the occurrence of a partial EMT phenotype. Mechanistically, TS enzymatic activity was found essential for the maintenance of the EMT/stem-like state by fueling a dihydropyrimidine dehydrogenase – dependent pyrimidine catabolism. In patient tissues, TS levels were found significantly higher in poorly differentiated and in triple negative BC, and strongly correlated with worse prognosis. The present study provides the rationale to study in-depth the role of NM at the crossroads of proliferation and differentiation, and depicts new avenues for the design of novel drug combinations for the treatment of BC

2019-02-01 | GSE122953 | GEO

Thymidylate synthase maintains the de-differentiated state of triple negative breast cancers.

Project description: Not available

| S-EPMC6888897 | biostudies-literature

Gene expression in cells expressing doxycycline-induced thymidylate synthase transgene

Project description:Gene expression was compared between a Tet-OFF transfomant expressing thymidylate synthase trasgene and its parental human colorectal cancer cell line, DLD-1, or the transformant exposed to doxycycline.

2015-03-31 | E-MTAB-3414 | biostudies-arrayexpress

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BRD4 signaling maintains the differentiated state of β cells [scRNA-seq]

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BRD4 signaling maintains the differentiated state of β cells [scATAC-seq]

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Epigenetic control of telomeric RNA maintains heterochromatin in telomerase-driven cancers

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