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The anticancer gene ORCTL3 targets stearoyl-CoA desaturase-1 for tumour-specific apoptosis.
- Source :
-
Oncogene [Oncogene] 2015 Mar 26; Vol. 34 (13), pp. 1718-28. Date of Electronic Publication: 2014 Apr 28. - Publication Year :
- 2015
-
Abstract
- ORCTL3 is a member of a group of genes, the so-called anticancer genes, that cause tumour-specific cell death. We show that this activity is triggered in isogenic renal cells upon their transformation independently of the cells' proliferation status. For its cell death effect ORCTL3 targets the enzyme stearoyl-CoA desaturase-1 (SCD1) in fatty acid metabolism. This is caused by transmembrane domains 3 and 4, which are more efficacious in vitro than a low molecular weight drug against SCD1, and critically depend on their expression level. SCD1 is found upregulated upon renal cell transformation indicating that its activity, while not impacting proliferation, represents a critical bottleneck for tumourigenesis. An adenovirus expressing ORCTL3 leads to growth inhibition of renal tumours in vivo and to substantial destruction of patients' kidney tumour cells ex vivo. Our results indicate fatty acid metabolism as a target for tumour-specific apoptosis in renal tumours and suggest ORCTL3 as a means to accomplish this.
- Subjects :
- Adenoviridae genetics
Animals
Cell Transformation, Neoplastic
Cells, Cultured
Endoplasmic Reticulum Stress
Female
Humans
Kidney Neoplasms pathology
Mice
Organic Anion Transporters physiology
Protein Structure, Tertiary
Apoptosis
Kidney Neoplasms therapy
Organic Anion Transporters genetics
Stearoyl-CoA Desaturase physiology
Subjects
Details
- Language :
- English
- ISSN :
- 1476-5594
- Volume :
- 34
- Issue :
- 13
- Database :
- MEDLINE
- Journal :
- Oncogene
- Publication Type :
- Academic Journal
- Accession number :
- 24769897
- Full Text :
- https://doi.org/10.1038/onc.2014.93