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BackgroundCancer cells present a sustained de novo fatty acid synthesis with an increase of saturated and monounsaturated fatty acid (MUFA) production. This change in fatty acid metabolism is associated with overexpression of stearoyl-CoA desaturase 1 (Scd1), which catalyses the transformation of saturated fatty acids into monounsaturated fatty acids (e.g., oleic acid). Several reports demonstrated that inhibition of Scd1 led to the blocking of proliferation and induction of apoptosis in cancer cells. Nevertheless, mechanisms of cell death activation remain to be better understood.Principal FindingsIn this study, we demonstrated that Scd1 extinction by siRNA triggered abolition of de novo MUFA synthesis in cancer and non-cancer cells. Scd1 inhibition-activated cell death was only observed in cancer cells with induction of caspase 3 activity and PARP-cleavage. Exogenous supplementation with oleic acid did not reverse the Scd1 ablation-mediated cell death. In addition, Scd1 depletion induced unfolded protein response (UPR) hallmarks such as Xbp1 mRNA splicing, phosphorylation of eIF2α and increase of CHOP expression. However, the chaperone GRP78 expression, another UPR hallmark, was not affected by Scd1 knockdown in these cancer cells indicating a peculiar UPR activation. Finally, we showed that CHOP induction participated to cell death activation by Scd1 extinction. Indeed, overexpression of dominant negative CHOP construct and extinction of CHOP partially restored viability in Scd1-depleted cancer cells.ConclusionThese results suggest that inhibition of de novo MUFA synthesis by Scd1 extinction could be a promising anti-cancer target by inducing cell death through UPR and CHOP activation.

International audienceUp-scaling silicon nanowire (SiNW)-based functionalities requires a reliable strategy to precisely position and integrate individual nanowires. We here propose an all-in-situ approach to fabricate self-positioned/aligned SiNW, via an in-plane solid-liquid-solid growth mode. Prototype field effect transistors, fabricated out of in-plane SiNWs using a simple bottom-gate configuration, demonstrate a hole mobility of 228 cm2/V s and on/off ratio >103. Further insight into the intrinsic doping and structural properties of these structures was obtained by laser-assisted 3 dimensional atom probe tomography and high resolution transmission electron microscopy characterizations. The results could provide a solid basis to deploy the SiNW functionalities in a cost-effective way