Lipogenesis in cancer progression (Review)

Abstract

Abstract. In normal tissues, energy-providing lipids come principally from circulating lipids. However, in growing tumors, energy supply is mainly provided by lipids coming from de novo synthesis. It is not surprising to see elevated expression of several lipogenic genes in tumors from different origins. The role of lipogenic genes in the establishment of the primary tumor has been clearly established. A large number of studies demonstrate a role of fatty acid synthase in the activation of cell cycle and inhibition of apoptosis in tumor cells. Other lipogenic genes such as the acetyl CoA carboxylase (ACC) and the stearoyl CoA desaturase 1 (SCD1) are highly expressed in primary tumors and also appear to play a role in their development. However, the role of lipogenesis in the metastatic process is less clear. In the present review, we aim to present the most recent evidences for the key role of lipogenic enzymes in the metastatic process and in epithelial to mesenchymal transition.

Acetyl-CoA carboxylase inhibition by ND-630 reduces hepatic steatosis, improves insulin sensitivity, and modulates dyslipidemia in rats

“…Altered fatty acid metabolism also is a hallmark of cancer and contributes to the abnormal and sustained cellular proliferation of malignancy (7,8). Therefore inhibition of FASyn and/or stimulation of FAOxn have the potential to affect these maladies favorably.…”

TRIM26 functions as a novel tumor suppressor of hepatocellular carcinoma and its downregulation contributes to worse prognosis

“…Cancer cells predominantly produce energy by a high rate of glycolysis in the cytosol, instead of a comparatively low rate of aerobic respiration characterized by oxidation of pyruvate in mitochondria in most normal cells [26]. The lipogenesis signaling is also continually activated (called de novo lipogenesis), and this is essential for the cells to obtain enough lipid for membrane synthesis during proliferation [27]. Accompanied by metabolic reprogramming, there is signaling transduction dysfunction, change of gene expression profile and change of sensitivity to chemotherapeutics [28].…”

“…Metabolic reprogramming is the hallmark of cancer cell and is crucial for tumor initiation, growth and metastasis [25]. This often includes increased glycolytic metabolism (Warburg effect) and lipogenesis relative to abnormal mitochondrial electron transport [26,27]. Cancer cells predominantly produce energy by a high rate of glycolysis in the cytosol, instead of a comparatively low rate of aerobic respiration characterized by oxidation of pyruvate in mitochondria in most normal cells [26].…”

Overexpression of the androgen receptor in human hepatoma cells and its effect on fatty acid metabolism

“…In general, cancer cells synthesize a high amount of fatty acids via increased expression, and subsequent activity, of lipogenic enzymes to fulfill their high energy requirements and to maintain cell membranes for growth (4,28,29). In patients with HCC, the alterations in lipid and lipoprotein metabolism can be clearly observed (30).…”