Expression and roles of fatty acid synthase in hepatocellular carcinoma

Abstract

Cell metabolism abnormalities are closely related to tumor occurrence and development. Fatty acid synthase (FASN) is the key molecule for catalyzing fatty acid synthesis. Increasing evidence indicates that FASN is highly expressed in a number of malignant tumors; it can promote the synthesis of endogenous fatty acids in tumor cells and then the synthesized fatty acids provide energy for the proliferation of tumor cells. However, there has been no systematic study focusing on FASN expression and function in hepatocellular carcinoma (HCC). The aim of the present study was to verify the high expression of FASN in HCC cells at the histological and cellular levels, and to construct FASN shRNA eukaryotic expression vector for interfering FASN expression in HCC cell line SK-Hep-1, in an effort to explore the role of FASN in the proliferation, apoptosis, invasion and migration of HCC cells. In the present study, we demonstrated that FASN was highly expressed in HCC tissues compared with tumor-adjacent tissue and normal liver cell line 7702 (P<0.05). FASN expression in the high metastatic MHCC97H and SK-Hep-1 cell lines was increased compared with low metastatic HCC cell lines (P<0.05). Then, we constructed a FASN shRNA eukaryotic expression vector; after HCC SK-Hep-1 cells were transfected, the cell proliferation, migration and invasion were inhibited, but FASN had no impact on the apoptosis of HCC cells. Collectively, these data indicate that FASN is possibly involved in the occurrence and metastasis of HCC. Thus, inhibition of FASN may be a promising approach for the treatment of HCC.

Oncogene dependent requirement of fatty acid synthase in hepatocellular carcinoma

“…[31][32][33] In accordance with previous data, we have found a progressive upregulation of FASN mRNA from human normal livers to HCC in our sample collection (Fig. 3A).…”

“…31,33,36 Specifically, silencing of FASN using siRNA or inhibition of FASN activity via the small molecule C75 led to decreased HCC cell proliferation and increased apoptosis. Mechanistically, it has been suggested that FASN may regulate the AKT 33 and p38MAPK 36 cascades.…”

Inactivation of fatty acid synthase impairs hepatocarcinogenesis driven by AKT in mice and humans

“…Also, levels of FASN and other lipogenic proteins as well as polymorphisms in lipogenic genes are associated with poor outcome in HCC patients [8–12]. In addition, FASN suppression has been shown to be detrimental for HCC growth in vitro [10,13,14]. Despite this body of evidence, key questions about FASN in HCC remain unanswered.…”

Chronic Liver Disease and the Detection of Hepatocellular Carcinoma by [18F]fluorocholine PET/CT

“…These tests rely primarily on structural-anatomic assessments as the basis of disease detection. With the emergence of precision medicine, it may also be useful to image liver tumors on the basis of molecular or metabolic traits, particularly if those traits can provide information on prognosis or treatment vulnerability [5–7]. …”