Cancer cells present sustained de novo fatty acid (FA) synthesis with increased production of saturated fatty acids (SFAs) and monounsaturated fatty acids (MUFAs). This change in FA metabolism is associated with overexpression of stearoyl-CoA desaturase 1 (SCD1), which catalyses the transformation of SFAs into MUFAs (e.g., oleic acid). In this study, we provide new evidence that SCD1 inhibition leads to the anti-proliferation effect of breast cancer cells through induction of apoptosis, cell cycle arrest and migration prevention. However, the antitumor effect of the SCD1 inhibitor can be reversed by exogenous oleic acid. We hypothesize that, in addition to de novo synthesis, cancer cells may uptake exogenous FAs actively. CD36, also known as FA translocase (FAT), that functions as a transmembrane protein and mediates the uptake of FAs, is observed to be highly expressed in breast cancer tissues. Furthermore, the anti-proliferation effect caused by the SCD1 inhibitor can not be reversed by exogenous oleic acid supplementation in CD36 knockdown breast cancer cells. Our study revealed that the lipid metabolism of breast cancer is regulated not only by de novo lipogenesis but also by the availability of lipids outside cancer cells. Consistent with FA synthesis, FA uptake and transport will be another important target pathway for anticancer therapy, and the FA channel protein CD36 may provide a promising therapeutic target. Lipogenesis combined with FA transport will be a new orientation for antitumor therapy.

BackgroundAlthough laparoscopic surgery has been recommended as an optional therapy for patients with early gastric cancer, whether patients with locally advanced gastric cancer (AGC) could benefit from laparoscopy-assisted distal gastrectomy (LADG) with D2 lymphadenectomy remains elusive due to a lack of comprehensive clinical data. To evaluate the efficacy of LADG, we conducted a multi-institutional randomized controlled trial to compare laparoscopy-assisted versus open distal gastrectomy (ODG) for AGC in North China.MethodsIn this RCT, after patients were enrolled according to the eligibility criteria, they were preoperatively assigned to LADG or ODG arm randomly with a 1:1 allocation ratio. The primary endpoint was the morbidity and mortality within 30 postoperative days to evaluate the surgical safety of LADG. The secondary endpoint was 3-year disease-free survival. This trial was registered at ClinicalTrial.gov as NCT02464215.ResultsBetween March 2014 and August 2017, a total of 446 patients with cT2-4aN0-3M0 (AJCC 7th staging system) were enrolled. Of these, 222 patients underwent LADG and 220 patients underwent ODG were included in the modified intention-to-treat analysis. The compliance rate of D2 lymph node dissection was identical between the LADG and ODG arms (99.5%, P = 1.000). No significant difference was observed regarding the overall postoperative complication rate in two groups (LADG 13.1%, ODG 17.7%, P = 0.174). No operation-related death occurred in both arms.ConclusionsThis trial confirmed that LADG performed by credentialed surgeons was safe and feasible for patients with AGC compared with conventional ODG.

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