Both de novo synthetized and exogenous fatty acids support the growth of hepatocellular carcinoma cells.
Although it is well established that fatty acids (FA) are indispensable for the proliferation and survival of cancer cells in hepatocellular carcinoma (HCC), inhibition of Fatty Acid Synthase (FASN) cannot completely repress HCC cell growth in culture. Thus, we hypothesized that uptake of exogenous FA by cancer cells might play an important role in the development and progression of HCC. Lipoprotein lipase (LPL) is the enzyme that catalyses the hydrolysis of triglycerides into free fatty acids (FFA) and increases the cellular uptake of FA.



We used immunohistochemistry and quantitative reverse transcription real-time polymerase chain reaction to evaluate LPL expression in human and mouse HCC samples. Using lipoprotein-deficient medium as well as siRNAs against LPL and/or FASN, we investigated whether human HCC cells depend on both endogenous and exogenous fatty acids for survival in vitro.



We found that LPL is upregulated in mouse and human HCC samples. High expression of LPL in human HCC samples is associated with poor prognosis. In HCC cell lines, silencing of FASN or LPL or culturing the cells in lipoprotein-deficient medium significantly decreased cell proliferation. Importantly, when FASN suppression was coupled to concomitant LPL depletion, the growth restraint of cell lines was further augmented.



The present study strongly suggests that both de novo synthetized and exogenous FA play a major role along hepatocarcinogenesis. Thus, combined suppression of LPL and FASN might be highly beneficial for the treatment of human HCC.
Department of Medical Oncology, Cancer Center, State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu, Sichuan, China.|Department of Bioengineering and Therapeutic Sciences and Liver Center, University of California, San Francisco, CA, USA.
Dan
D
Cao
Department of Bioengineering and Therapeutic Sciences and Liver Center, University of California, San Francisco, CA, USA.|Department of Nutrition and Health, College of Food Science and Nutritional Engineering, China Agricultural University, Beijing, China.
Xinhua
X
Song
Department of Bioengineering and Therapeutic Sciences and Liver Center, University of California, San Francisco, CA, USA.
Li
0000-0001-7971-8725
L
Che
Department of Bioengineering and Therapeutic Sciences and Liver Center, University of California, San Francisco, CA, USA.|Department of Hepatobiliary Surgery, Xijing Hospital, The Fourth Military Medical University, Xi'an, Shaanxi, China.
Xiaolei
X
Li
Department of Clinical and Experimental Medicine, University of Sassari, Sassari, Italy.
Maria G
MG
Pilo
Department of Clinical and Experimental Medicine, University of Sassari, Sassari, Italy.
Gianpaolo
G
Vidili
Department of Clinical and Experimental Medicine, University of Sassari, Sassari, Italy.
Alberto
A
Porcu
Department of Biomedical Sciences, University of Sassari, Sassari, Italy.
Antonio
A
Solinas
Institute of Pathology, University Medicine Greifswald, Greifswald, Germany.
Antonio
A
Cigliano
Department of Clinical and Experimental Medicine, University of Sassari, Sassari, Italy.
Giovanni M
GM
Pes
Institute of Pathology, University Medicine Greifswald, Greifswald, Germany.
Silvia
S
Ribback
Institute of Pathology, University Medicine Greifswald, Greifswald, Germany.
Frank
F
Dombrowski
Department of Bioengineering and Therapeutic Sciences and Liver Center, University of California, San Francisco, CA, USA.
Xin
X
Chen
School of Pharmacy, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China.
Lei
L
Li
Department of Clinical and Experimental Medicine, University of Sassari, Sassari, Italy.
Diego F
DF
Calvisi
D000818:Animals; D006528:Carcinoma, Hepatocellular / Q000378:metabolism* / Q000473:pathology; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D054890:Fatty Acid Synthase, Type I / Q000235:genetics / Q000378:metabolism*; D005227:Fatty Acids / Q000378:metabolism*; D006801:Humans; D008071:Lipoprotein Lipase / Q000235:genetics / Q000378:metabolism*; D008113:Liver Neoplasms / Q000378:metabolism* / Q000473:pathology; D051379:Mice; D015999:Multivariate Analysis; D016016:Proportional Hazards Models; D034741:RNA, Small Interfering / Q000235:genetics; D015398:Signal Transduction / Q000187:drug effects; D014280:Triglycerides / Q000378:metabolism; D015854:Up-Regulation
D005227:Fatty Acids; D034741:RNA, Small Interfering; D014280:Triglycerides; C518729:FASN protein, human; D054890:Fatty Acid Synthase, Type I; C548261:LPL protein, human; D008071:Lipoprotein Lipase
fatty acid synthase; hepatocellular carcinoma; lipogenesis; lipoprotein lipase