Glucose-regulated protein of 94 kDa contributes to the development of an aggressive phenotype in breast cancer cells - 11/07/18
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Graphical abstract |
Highlights |
• | Hypoxia does not induce the expression of Grp94 in cancer cells. |
• | Glucose deprivation increases the expression levels of Grp94 in breast cancer cells. |
• | Silencing Grp94 gene leads to a less aggressive phenotype in breast cancer cells. |
• | Grp94 knock-down enhances apoptosis by doxorubicin in breast cancer cells. |
Abstract |
Grp94 plays an essential role in protein assembly. We previously suggested that Grp94 overexpression is involved in tumor aggressiveness. However, the underlying mechanisms remain unknown. Since many tumors display high Grp94 levels, we investigated the effects of tumor microenvironment on the regulation of this chaperone expression. First, we found out that hypoxia did not change Grp94 expression in the human tumor cell lines MCF-7 (breast cancer) and HepG2 (liver cancer). Second, glucose deprivation significantly increased Grp94 protein levels. Subsequently, we focused in the putative role of Grp94 in the acquisition of an aggressive phenotype by cancer cells. Using a more aggressive cancer cell model (MDA-MB-231 breast tumor cells), we found out that Grp94 knockdown using siRNA decreased the invasive capacity of cancer cells. Moreover, cells with decreased Grp94 levels displayed an enhanced sensitivity of tumor cells to doxorubicin, a standard drug in the treatment of breast cancer. Taken together, our results suggest that the expression of Grp94 is linked to tumor aggressiveness. Therefore, targeting Grp94 could be an effective way to inhibit tumor growth improving chemotherapy outcome.
Le texte complet de cet article est disponible en PDF.Abbreviations : eIF2, ER, Grp94, Grp78, HIF-1α, HRE, Hsp, UPR
Chemical compounds studied in this article : Cobalt chloride (PubChem CID: 24288), Doxorubicin (PubChem CID: 443939), Staurosporine (PubChem CID: 44259)
Keywords : Grp94, Cancer cells, Hypoxia, Glucose, Aggressive phenotype, Invasion, Doxorubicin
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Vol 105
P. 115-120 - septembre 2018 Retour au numéroBienvenue sur EM-consulte, la référence des professionnels de santé.
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