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Huang M, Koizumi A, Narita S, et al. Diet-induced alteration of fatty acid synthase in prostate cancer progression. Oncogenesis. 2016;5:e195doi: 10.1038/oncsis.2015.42.
Huang, M., Koizumi, A., Narita, S., Inoue, T., Tsuchiya, N., Nakanishi, H., Numakura, K., Tsuruta, H., Saito, M., Satoh, S., Nanjo, H., Sasaki, T., & Habuchi, T. (2016). Diet-induced alteration of fatty acid synthase in prostate cancer progression. Oncogenesis, 5e195. https://doi.org/10.1038/oncsis.2015.42
Huang, M, et al. "Diet-induced alteration of fatty acid synthase in prostate cancer progression." Oncogenesis vol. 5 (2016): e195. doi: https://doi.org/10.1038/oncsis.2015.42
Huang M, Koizumi A, Narita S, Inoue T, Tsuchiya N, Nakanishi H, Numakura K, Tsuruta H, Saito M, Satoh S, Nanjo H, Sasaki T, Habuchi T. Diet-induced alteration of fatty acid synthase in prostate cancer progression. Oncogenesis. 2016 Feb 15;5:e195. doi: 10.1038/oncsis.2015.42. PMID: 26878389; PMCID: PMC5154344.
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Oncogenesis. 2016 Feb 15;5:e195. doi: 10.1038/oncsis.2015.42.

Diet-induced alteration of fatty acid synthase in prostate cancer progression.

Oncogenesis

M Huang, A Koizumi, S Narita, T Inoue, N Tsuchiya, H Nakanishi, K Numakura, H Tsuruta, M Saito, S Satoh, H Nanjo, T Sasaki, T Habuchi

Affiliations

  1. Department of Urology, Akita University Graduate School of Medicine, Akita, Japan.
  2. AMED-CREST, Japan Agency for Medical Research and Development (AMED), Tokyo, Japan.
  3. Research Center for Biosignal,Akita University Graduate School of Medicine, Akita, Japan.
  4. Department of Clinical Pathology, Akita University Graduate School of Medicine, Akita, Japan.

PMID: 26878389 PMCID: PMC5154344 DOI: 10.1038/oncsis.2015.42

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.

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