Regulation of fatty acid synthesis in immune cells.

Metabolic reprogramming plays a critical role in the important cellular metabolic alterations that occur during the activation of immune cells to enable them to adapt to the extracellular environment. Here, we review recent studies on how substrate availability and metabolites mediate the signalling pathways that regulate fatty acid synthesis (FAS) in different immune cells and how FAS determines cellular fate and function. The major regulators sterol regulatory element-binding proteins and liver X receptors, the key enzyme ATP citrate lyase and the PI3K-Akt-mTOR signalling axis play important roles in de novo FAS during a variety of biological events, including cellular proliferation and differentiation and the development of organelles and intracellular membrane components in immune cells. In addition, the regulation of FAS substantially contributes to the inflammatory response of immune cells. Post-transcriptional modifications in FAS are also closely associated with the functional processes of immune cells. Understanding and investigating the intrinsic regulatory mechanism of FAS is of great significance for developing novel therapies for inflammation-induced diseases.

ATP citrate lyase expression is associated with advanced stage and prognosis in gastric adenocarcinoma.

Gastric adenocarcinoma (GA) is one of the most common cancer worldwide. ATP citrate lyase (ACLY) is generally recognized as a key enzyme of de novo fatty acid synthesis responsible for generation of oxaloacetate and cytosolic acetyl-CoA. This study aimed to investigate the expression level of ACLY in GA and evaluate the relationship between ACLY expression and the prognosis of GA patients. Paraffin archived samples from 83 GA patients were used to analyze ACLY expression by immunohistochemistry. ACLY was significantly upregulated in GA tissues compared with adjacent normal tissues (P < 0.001). High ACLY expression was correlated with advanced stages (P = 0.007) and lymph node metastasis (P = 0.022). Furthermore, patients with low ACLY expression had longer survival time than those with high ACLY expression (P = 0.031). In conclusion, these results indicate that ACLY might serve as a biomarker to predict the progression and prognosis of GA patients.

RASAL1 attenuates gastric carcinogenesis in nude mice by blocking RAS/ERK signaling.

Recent studies have suggested that the RAS protein activator like-1 (RASAL1) functions as a tumor suppressor in vitro and may play an important role in the development of gastric cancer. However, whether or not RASAL1 suppresses tumor growth in vivo remains to be determined. In the present study, we investigated the role of RASAL1 in gastric carcinogenesis using an in vivo xenograft model. A lentiviral RASAL1 expression vector was constructed and utilized to transfect the human poorly differentiated gastric adenocarcinoma cell line, BGC-823. RASAL1 expression levels were verified by quantitative real-time RT-PCR and Western blotting analysis. Then, we established the nude mice xenograft model using BGC-823 cells either over-expressing RASAL1 or normal. After three weeks, the results showed that the over-expression of RASAL1 led to a significant reduction in both tumor volume and weight compared with the other two control groups. Furthermore, in xenograft tissues the increased expression of RASAL1 in BGC-823 cells caused decreased expression of p-ERK1/2, a downstream moleculein the RAS/RAF/MEK/ERK signal pathway. These findings demonstrated that the over-expression of RASAL1 could inhibit the growth of gastric cancer by inactivation of the RAS/RAF/MEK/ERK pathway in vivo. This study indicates that RASAL1 may attenuate gastric carcinogenesis.