作者: Ghada AbuAli , Stefan Grimm
DOI: 10.1007/978-1-4471-6458-6_11
关键词: Endoplasmic reticulum 、 Kidney metabolism 、 Molecular biology 、 Biology 、 Organic cation transport proteins 、 Unfolded protein response 、 Apoptosis 、 Cancer cell 、 Ex vivo 、 Stearoyl-CoA desaturase-1
摘要: ORCTL3, an organic cation/anion transporter expressed in various tissue types, was isolated a genome-wide cDNA screen as gene with tumor-specific apoptosis activity. When overexpressed it elicits response many transformed cells, while normal cells remain unaffected. It can be activated for induction by individual tumorigenic mutations renal cells. This effect is independent of the tumor cells’ proliferation status and mediated incomplete ER stress response, characterized accumulation endoplasmic reticulum-stress marker ATF4, but not BiP. Recent studies show that its activity ORCTL3 targets enzyme stearoyl-CoA desaturase-1 (SCD-1) involved fatty acid metabolism. evidenced inhibition induced through when SCD-1 product oleic exogenously supplemented or co-transfected ORCTL3’s to specifically target caused transmembrane domains 3 4 mouse, human, gene. In vivo model shows significant shrinkage size xenograft tumors injected adenoviral carrier carrying mouse An ex study using human cancer confirmed promising ORCTL3. Since metabolism induces these reveals novel therapeutic interference option