Dataset Information

Elucidation of the molecular changes underlying abnormal ER characteristic of osteosarcoma

ABSTRACT: Pediatric osteosarcomas are characterized by an unusually dilated endoplasmic reticulum (ER). Our analysis of RNA expression data from 108 patient tumor samples and patient-derived xenografts (PDXs) revealed the overwhelming majority of these tumor have reduced expression of four COPII vesicle components that trigger aberrant accumulation of procollagen-I protein within the ER. CRISPR activation technology was used to increase expression of two of these, SAR1A and SEC24D, to physiologically normal levels. This was sufficient to resolve the dilated ER morphology and restore secretion of collagen-I, as well as enhance secretion of extracellular matrix (ECM) proteins. Our studies reveal the mechanism responsible for the dilated ER that is a hallmark characteristic of OS and identify a highly conserved molecular signature for this genetically unstable tumor.

INSTRUMENT(S): LTQ Orbitrap Elite

ORGANISM(S): Homo Sapiens (human)

SUBMITTER: Yuxin Li

LAB HEAD: Junmin Peng

PROVIDER: PXD031620 | Pride | 2022-05-20

REPOSITORIES: Pride

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Dataset's files

Source:

			Action	DRS
	Hendegrp_060420_ip_b1.1.pepcXML	Other
	Hendegrp_060420_ip_b1.raw	Raw
	Hendegrp_060420_ip_b2.1.pepcXML	Other
	Hendegrp_060420_ip_b2.raw	Raw
	Hendegrp_060420_ip_b3.1.pepcXML	Other

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Publications

Secretory defects in pediatric osteosarcoma result from downregulation of selective COPII coatomer proteins.

Wood Rachael K RK Flory Ashley R AR Mann Melissa J MJ Talbot Lindsay J LJ Hendershot Linda M LM

iScience 20220317 4

Pediatric osteosarcomas (OS) exhibit extensive genomic instability that has complicated the identification of new targeted therapies. We found the vast majority of 108 patient tumor samples and patient-derived xenografts (PDXs), which display an unusually dilated endoplasmic reticulum (ER), have reduced expression of four COPII vesicle components that trigger aberrant accumulation of procollagen-I protein within the ER. CRISPR activation technology was used to increase the expression of two of t ...[more]

PMID: 35402877

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