Novel lipogenic enzyme ELOVL7 is involved in prostate cancer growth through saturated long-chain fatty acid metabolism.
A number of epidemiologic studies have indicated a strong association between dietary fat intake and prostate cancer development, suggesting that lipid metabolism plays some important roles in prostate carcinogenesis and its progression. In this study, through our genome-wide gene expression analysis of clinical prostate cancer cells, we identified a novel lipogenic gene, ELOVL7, coding a possible long-chain fatty acid elongase, as overexpressed in prostate cancer cells. ELOVL7 expression is regulated by the androgen pathway through SREBP1, as well as other lipogenic enzymes. Knockdown of ELOVL7 resulted in drastic attenuation of prostate cancer cell growth, and it is notable that high-fat diet promoted the growth of in vivo tumors of ELOVL7-expressed prostate cancer. In vitro fatty acid elongation assay and fatty acid composition analysis indicated that ELOVL7 was preferentially involved in fatty acid elongation of saturated very-long-chain fatty acids (SVLFA, C20:0 approximately ). Lipid profiles showed that knockdown of ELOVL7 in prostate cancer cells affected SVLFAs in the phospholipids and the neutral lipids, such as cholesterol ester. Focusing on cholesterol ester as a source of de novo steroid synthesis, we show that ELOVL7 affected de novo androgen synthesis in prostate cancer cells. These findings suggest that EVOLV7 could be involved in prostate cancer growth and survival through the metabolism of SVLFAs and their derivatives, could be a key molecule to elucidate the association between fat dietary intake and prostate carcinogenesis, and could also be a promising molecular target for development of new therapeutic or preventive strategies for prostate cancers.
Tamura
Kenji
K
Laboratory of Molecular Medicine, Human Genome Center, Institute of Medical Science, The University of Tokyo, Tokyo, Japan.
Makino
Asami
A
Hullin-Matsuda
Françoise
F
Kobayashi
Toshihide
T
Furihata
Mutsuo
M
Chung
Suyoun
S
Ashida
Shingo
S
Miki
Tsuneharu
T
Fujioka
Tomoaki
T
Shuin
Taro
T
Nakamura
Yusuke
Y
Nakagawa
Hidewaki
H
D000123:Acetyltransferases / Q000502:physiology*; D000728:Androgens / Q000494:pharmacology; D000818:Animals; D014408:Biomarkers, Tumor; D015152:Blotting, Northern; D002853:Chromatography, Liquid; D004041:Dietary Fats; D000081031:Fatty Acid Elongases; D005227:Fatty Acids / Q000378:metabolism*; D008401:Gas Chromatography-Mass Spectrometry; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007074:Immunoglobulin G / Q000276:immunology; D050356:Lipid Metabolism; D008297:Male; D051379:Mice; D008819:Mice, Nude; D008969:Molecular Sequence Data; D009376:Neoplasms, Hormone-Dependent / Q000378:metabolism / Q000473:pathology*; D020411:Oligonucleotide Array Sequence Analysis; D010446:Peptide Fragments / Q000378:metabolism; D011471:Prostatic Neoplasms / Q000378:metabolism / Q000473:pathology*; D011817:Rabbits; D051780:Sterol Regulatory Element Binding Protein 1 / Q000235:genetics / Q000378:metabolism; D053719:Tandem Mass Spectrometry; D014407:Tumor Cells, Cultured; D023041:Xenograft Model Antitumor Assays
D000728:Androgens; D014408:Biomarkers, Tumor; D004041:Dietary Fats; C000630957:ELOVL7 protein, human; C000630963:Elovl7 protein, mouse; D005227:Fatty Acids; D007074:Immunoglobulin G; D010446:Peptide Fragments; C497387:SREBF1 protein, human; D051780:Sterol Regulatory Element Binding Protein 1; D000123:Acetyltransferases; D000081031:Fatty Acid Elongases