GRP94 Is Involved in the Lipid Phenotype of Brain Metastatic Cells.
Int J Mol Sci
; 20(16)2019 Aug 09.
Article
in En
| MEDLINE
| ID: mdl-31395819
ABSTRACT
Metabolic adaptation may happen in response to the pressure exerted by the microenvironment and is a key step in survival of metastatic cells. Brain metastasis occurs as a consequence of the systemic dissemination of tumor cells, a fact that correlates with poor prognosis and high morbidity due to the difficulty in identifying biomarkers that allow a more targeted therapy. Previously, we performed transcriptomic analysis of human breast cancer patient samples and evaluated the differential expression of genes in brain metastasis (BrM) compared to lung, bone and liver metastasis. Our network approach identified upregulation of glucose-regulated protein 94 (GRP94) as well as proteins related to synthesis of fatty acids (FA) in BrM. Here we report that BrM cells show an increase in FA content and decreased saturation with regard to parental cells measured by Raman spectroscopy that differentiate BrM from other metastases. Moreover, BrM cells exerted a high ability to oxidize FA and compensate hypoglycemic stress due to an overexpression of proteins involved in FA synthesis and degradation (SREBP-1, LXRα, ACOT7). GRP94 ablation restored glucose dependence, down-regulated ACOT7 and SREBP-1 and decreased tumorigenicity in vivo. In conclusion, GRP94 is required for the metabolic stress survival of BrM cells, and it might act as a modulator of lipid metabolism to favor BrM progression.
Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Brain Neoplasms
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Breast Neoplasms
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HSP70 Heat-Shock Proteins
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Fatty Acids
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Membrane Proteins
Limits:
Animals
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Female
/
Humans
Language:
En
Journal:
Int J Mol Sci
Year:
2019
Document type:
Article
Affiliation country: