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Cancer cell-secreted spermidine synthase induces skeletal muscle fibrosis upon radiotherapy (MDA-MB-231)

ABSTRACT: Cancer cell-secreted spermidine synthase induces skeletal muscle fibrosis upon radiotherapy (MDA-MB-231)

PROVIDER: PRJNA1097655 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR28591625_1.fastq.gz	Fastqsanger.gz
	SRR28591625_2.fastq.gz	Fastqsanger.gz
	SRR28591626_1.fastq.gz	Fastqsanger.gz
	SRR28591626_2.fastq.gz	Fastqsanger.gz
	SRR28591627_1.fastq.gz	Fastqsanger.gz

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Cancer cell-secreted spermidine synthase induces skeletal muscle fibrosis upon radiotherapy (MDA-MB-231)

Project description:Radiotherapy (RT) reduces the risk of cancer recurrence and death, while accompanied by multiple side effects including muscle fibrosis and weakness, seriously affects the life quality of patients. However, the underlying mechanism is poorly defined. Here, we identify cancer cells secrete more spermidine synthase (SRM) enzyme through small extracellular vesicles (sEVs) to trigger skeletal muscle weakness upon RT. Mechanistically, RT-triggered arachidonic acid (ArA) accumulation elevates the ISGylation of SRM protein, facilitating SRM packaging into EVs from primary tumor. Circulating SRM results in spermidine accumulation in skeletal muscle and type I collagen fiber biosynthesis in an eIF5A-dependent manner. However, losartan treatment blocks the ISGylation of SRM and its subsequent secretion. Collectively, our findings determine that ArA functions in concert for circulating SRM secretion upon RT, which aggravates skeletal muscle fibrosis through rewiring polyamine metabolism, shedding light on the alleviation of RT-mediated muscle weakness when combined with losartan treatment.

2025-04-03 | GSE263505 | GEO

Cancer cell-secreted spermidine synthase induces skeletal muscle fibrosis upon radiotherapy (Gastrocnemius muscle)

Project description:Cancer cell-secreted spermidine synthase induces skeletal muscle fibrosis upon radiotherapy (Gastrocnemius muscle)

| PRJNA1097658 | ENA

Cancer cell-secreted spermidine synthase induces skeletal muscle fibrosis upon radiotherapy (Xenograft tumor)

Project description:Cancer cell-secreted spermidine synthase induces skeletal muscle fibrosis upon radiotherapy (Xenograft tumor)

| PRJNA1097659 | ENA

Cancer cell-secreted spermidine synthase induces skeletal muscle fibrosis upon radiotherapy (Gastrocnemius muscle KD)

Project description:Cancer cell-secreted spermidine synthase induces skeletal muscle fibrosis upon radiotherapy (Gastrocnemius muscle KD)

| PRJNA1097657 | ENA

Cancer cell-secreted spermidine synthase induces skeletal muscle fibrosis upon radiotherapy (Gastrocnemius muscle)

2025-04-03 | GSE263507 | GEO

Cancer cell-secreted spermidine synthase induces skeletal muscle fibrosis upon radiotherapy (Xenograft tumor)

2025-04-03 | GSE263506 | GEO

Cancer cell-secreted spermidine synthase induces skeletal muscle fibrosis upon radiotherapy (Gastrocnemius muscle KD)

2025-04-03 | GSE263508 | GEO

Arachidonic acid triggers spermidine synthase secretion from primary tumor to induce skeletal muscle weakness upon irradiation

Project description:Radiotherapy (RT) reduces the risk of cancer recurrence and death, while accompanied by multiple side effects including muscle weakness, seriously affects the life quality of patients. However, the underlying mechanism is not well defined. Here, we identify cancer cells secrete more spermidine synthase (SRM) protein through small extracellular vesicles (sEVs) to trigger skeletal muscle weakness upon RT. Mechanistically, RT-triggered arachidonic acid (ArA) accumulation elevates the ISGylation of SRM protein, facilitating SRM package into EVs from primary tumor. Circulating SRM proteins enhance spermidine accumulation in skeletal muscle and type I collagen fibers biosynthesis in an eIF5A-dependent manner. Deposition of randomly aligned collogen fibers induced by SRM+ EVs results in skeletal muscle fibrosis and weakness, as well as bone matrix loss. However, losartan treatment blocks the ISGylation of SRM and its subsequent secretion. Collectively, our findings determine that ArA functions in concert for circulating SRM secretion upon RT, which aggravates skeletal muscle fibrosis through rewiring polyamine metabolism, shedding light on the alleviation of RT-mediated muscle weakness when combined with losartan treatment.

2025-04-03 | GSE285652 | GEO

Spermidine synthase regulates extracellular vesicle secretion in castration resistant prostate cancer.

Project description:Spermidine synthase regulates extracellular vesicle secretion in castration resistant prostate cancer.

| PRJNA600204 | ENA

Spermidine Yeast Aging Array

Project description:Administration of spermidine, a natural polyamine whose intracellular concentration declines during human ageing, markedly extends the lifespan of various model organisms including yeast, flies and worms. In ageing yeast, spermidine treatment triggeres epigenetic deacetylation of histone H3 through inhibition of histone acetyltransferases (HAT), leading to induction of autophagy and thereby suppressing oxidative stress and necrosis. In order to further characterize the effects by spermidine supplementation of aging yeast cultures and to understand how global histone deacetylation affects gene transcription during aging, Affymetrix-based microarray analyses of three day old as well as ten day old cultures with and without administration of spermidine was performed.

2012-01-04 | E-MTAB-912 | biostudies-arrayexpress

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