title: Diet-induced alteration of fatty acid synthase in prostate cancer progression.
abstract: Fatty acid synthase (FASN) is a cytosolic metabolic enzyme that catalyzes de novo fatty acid synthesis. A high-fat diet (HFD) is attributed to prostate cancer (PCa) progression, but the role FASN on HFD-mediated PCa progression remains unclear. We investigated the role of FASN on PCa progression in LNCaP xenograft mice fed with HFD or low-fat diet (LFD), in PCa cells, and in clinical PCa. The HFD promoted tumour growth and FASN expression in the LNCaP xenograft mice. HFD resulted in AKT and extracellular signal-regulated kinase (ERK) activation and 5' adenosine monophosphate-activated protein kinase (AMPK) inactivation. Serum FASN levels were significantly lower in the HFD group (P=0.026) and correlated inversely with tumour volume (P=0.022). Extracellular FASN release was enhanced in the PCa cells with phosphatidylinositol 3-kinase (PI3K)/mitogen-activated protein kinase (MAPK) inhibition and AMPK signalling activation. FASN inhibition resulted in decrease of PCa cell proliferation through PI3K/MAPK downregulation and AMPK activation. Furthermore, AMPK activation was associated with FASN downregulation and PI3K/MAPK inactivation. Clinically, high FASN expression was significantly associated with high Gleason scores and advanced pathological T stage. Moreover, FASN expression was markedly decreased in the PCa response to androgen deprivation therapy and chemotherapy. HFD modulates FASN expression, which may be an important mechanism in HFD-associated PCa progression. Furthermore, a critical stimulatory loop exists between FASN and the PI3K/MAPK system, whereas AMPK signalling was associated with suppression. These may offer appropriate targets for chemoprevention and cancer therapy in HFD-induced PCa.
authors.affiliation: Department of Urology, Akita University Graduate School of Medicine, Akita, Japan.|AMED-CREST, Japan Agency for Medical Research and Development (AMED), Tokyo, Japan.
authors.forename: M
authors.initials: M
authors.lastname: Huang
authors.affiliation: Department of Urology, Akita University Graduate School of Medicine, Akita, Japan.|AMED-CREST, Japan Agency for Medical Research and Development (AMED), Tokyo, Japan.
authors.forename: A
authors.initials: A
authors.lastname: Koizumi
authors.affiliation: Department of Urology, Akita University Graduate School of Medicine, Akita, Japan.|AMED-CREST, Japan Agency for Medical Research and Development (AMED), Tokyo, Japan.
authors.forename: S
authors.initials: S
authors.lastname: Narita
authors.affiliation: Department of Urology, Akita University Graduate School of Medicine, Akita, Japan.|AMED-CREST, Japan Agency for Medical Research and Development (AMED), Tokyo, Japan.
authors.forename: T
authors.initials: T
authors.lastname: Inoue
authors.affiliation: Department of Urology, Akita University Graduate School of Medicine, Akita, Japan.
authors.forename: N
authors.initials: N
authors.lastname: Tsuchiya
authors.affiliation: Research Center for Biosignal,Akita University Graduate School of Medicine, Akita, Japan.
authors.forename: H
authors.initials: H
authors.lastname: Nakanishi
authors.affiliation: Department of Urology, Akita University Graduate School of Medicine, Akita, Japan.
authors.forename: K
authors.initials: K
authors.lastname: Numakura
authors.affiliation: Department of Urology, Akita University Graduate School of Medicine, Akita, Japan.
authors.forename: H
authors.initials: H
authors.lastname: Tsuruta
authors.affiliation: Department of Urology, Akita University Graduate School of Medicine, Akita, Japan.
authors.forename: M
authors.initials: M
authors.lastname: Saito
authors.affiliation: Department of Urology, Akita University Graduate School of Medicine, Akita, Japan.
authors.forename: S
authors.initials: S
authors.lastname: Satoh
authors.affiliation: Department of Clinical Pathology, Akita University Graduate School of Medicine, Akita, Japan.
authors.forename: H
authors.initials: H
authors.lastname: Nanjo
authors.affiliation: AMED-CREST, Japan Agency for Medical Research and Development (AMED), Tokyo, Japan.|Research Center for Biosignal,Akita University Graduate School of Medicine, Akita, Japan.
authors.forename: T
authors.initials: T
authors.lastname: Sasaki
authors.affiliation: Department of Urology, Akita University Graduate School of Medicine, Akita, Japan.|AMED-CREST, Japan Agency for Medical Research and Development (AMED), Tokyo, Japan.
authors.forename: T
authors.initials: T
authors.lastname: Habuchi