10q24.31

FADS5,MSTP008,SCD1,SCDOS,hSCD1

Breast cancer

Over-expression of SCD1 is associated with enhanced growth rate of breast cancer cell lines and shorter overall survival and relapse-free survival (RFS) in breast cancer patients (Holder et al., 2013). Furthermore, it is demonstrated that high desaturation index has a negative correlation with the risk of breast cancer (Chajs et al., 1999). Down-regulation of SCD1 by specific siRNA also leads to reduction of proliferation rate, cell cycles gene expression and phosphorylation state of ERK1/2 (Mauvoisin, Charfi, Lounis, Rassart, & Mounier, 2013). On the other hand, Mohammadzadeh et al. study revealed that inhibition of SCD1 by a selective inhibitor causes significant alteration in fatty acid composition of tissue cultured breast carcinoma in comparison to normal-appearing breast tissues and this has been attributed to the different level of SCD1 activity (Mohammadzadeh et al., 2014).

Hepatocellular carcinoma

Bansal et al. study indicated that SCD1 was significantly over-expressed in hepatocellular carcinoma (HCC) tissues in comparison to adjacent normal tissues and in HCC cell lines including HepG2, Hep3B and PLC/PLF/5. Furthermore, the level of SCD1 was negatively associated with tumour differentiation grade. Treatment of liver cancer cell lines with different panel of chemotherapeutic agents also caused over expression of SCD1 in a time dependent manner and the consequent resistance to drug induced apoptosis. It is also demonstrated that inhibition of SCD1 by genetic manipulation or chemical inhibitors leads to elevated sensitivity to chemotherapeutic agents (Bansal et al., 2013).

Colorectal cancer

Recent studies have revealed that cell death is induced in colorectal cancer cells following SCD1 inhibition. This effect is most possibly mediated through caspase 3 activity and PPAR-cleavage (Minville-Walz et al., 2010). Other studies have also reported that HTC116 colon cancer cell lines are susceptible to SCD1 depletion and subsequent decreased cell viability (Mason et al., 2012).

Esophageal cancer

Shuai Guo et al. study has shown SCD1 up-regulation in esophageal cancerous tissues in comparison to adjacent normal tissues. Furthermore, tissue lipid distribution analysis revealed that MUFA/PUFA ratio is elevated in cancerous microenvironment due to over activation of SCD1 (Guo, Wang, Zhou, & Li, 2014).

Gastric cancer

Roongta et al. reported SCD1 inhibition causes tumour growth delay in a xenograft model in nude mice (Roongta et al., 2011).

Obesity

Obesity and type 2 diabetes are highly associated with abnormal lipid metabolism and intramyocellular accumulation of triglycerides. Hulver et al reported that SCD1 is up-regulated in skeletal myocytes of obese individuals. Overexpression and overactivity of SCD1 is linked to lower fatty acid ?-oxidation rate and elevation of triglyceride and MUFA synthesis in extremely obese population (Hulver et al., 2005).

Lipotoxicity and inflammation

Lipotoxicity is a common characteristic of diabetes and metabolic syndrome. It is defined by the elevation of intracellular fatty acid metabolites including diacylglycerol and ceramides leading to endoplasmic reticulum (ER) stress. This cellular stress triggers phosphorylation of insulin receptor substrates in serine/threonine residues and activation of the nuclear factor (NF)-?B pathway (Eizirik, Cardozo, & Cnop, 2008). Such signalling pathways induce an acute inflammatory response with cytokines secretion and diminished down-stream events of insulin receptor signalling cascade resulting in low-grade inflammatory state (Peter et al., 2009). Among SFA, stearate and palmitate have a high lipotoxicity potential to induce inflammation, ER stress and insulin resistance (Staiger et al., 2006). SCD1 enzyme desaturases stearate and palmitate to less toxic monounsaturated forms oleate and palmitoleate (Peter et al., 2008). Overexpression of SCD1 is also associated with increased triglyceride storage and decreased palmitate-induced apoptosis, ceramide and diacylglycerol synthesis, as well as insulin resistance (Pinnamaneni, Southgate, Febbraio, & Watt, 2006).