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Altering phosphoinositides in high‐fat diet‐associated prostate tumor xenograft growth

The metabolic reprogramming of phospholipids may affect intracellular signal transduction pathways. A high‐fat diet (HFD) is attributed to prostate cancer (PCa) progression, but the expression pattern and role of phospholipids in HFD‐mediated PCa progression remains unclear. In this study, HFD enhan...

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Autores principales: Huang, Mingguo, Koizumi, Atsushi, Narita, Shintaro, Nakanishi, Hiroki, Sato, Hiromi, Kashima, Soki, Nara, Taketoshi, Kanda, Sohei, Numakura, Kazuyuki, Saito, Mitsuru, Satoh, Shigeru, Nanjo, Hiroshi, Sasaki, Takehiko, Habuchi, Tomonori
Formato: Online Artículo Texto
Lenguaje:English
Publicado: John Wiley and Sons Inc. 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8706770/
https://www.ncbi.nlm.nih.gov/pubmed/34977875
http://dx.doi.org/10.1002/mco2.89
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author Huang, Mingguo
Koizumi, Atsushi
Narita, Shintaro
Nakanishi, Hiroki
Sato, Hiromi
Kashima, Soki
Nara, Taketoshi
Kanda, Sohei
Numakura, Kazuyuki
Saito, Mitsuru
Satoh, Shigeru
Nanjo, Hiroshi
Sasaki, Takehiko
Habuchi, Tomonori
author_facet Huang, Mingguo
Koizumi, Atsushi
Narita, Shintaro
Nakanishi, Hiroki
Sato, Hiromi
Kashima, Soki
Nara, Taketoshi
Kanda, Sohei
Numakura, Kazuyuki
Saito, Mitsuru
Satoh, Shigeru
Nanjo, Hiroshi
Sasaki, Takehiko
Habuchi, Tomonori
author_sort Huang, Mingguo
collection PubMed
description The metabolic reprogramming of phospholipids may affect intracellular signal transduction pathways. A high‐fat diet (HFD) is attributed to prostate cancer (PCa) progression, but the expression pattern and role of phospholipids in HFD‐mediated PCa progression remains unclear. In this study, HFD enhanced LNCaP xenograft tumor growth by upregulating the phosphatidylinositol (PI) 3‐kinase (PI3K)/AKT signaling pathway. A lipidomic analysis using xenograft tumors showed that phosphoinositides, especially PI (3,4,5)‐trisphosphate (PIP(3)), including several species containing C38:4, C38:3, and C40:4 fatty acids, increased in the HFD group compared to control. Fatty acid synthase (FASN) was significantly upregulated in xenograft tumors under HFD in both gene and protein levels. PCa cell growth was significantly inhibited through the decreased AKT signaling pathway by treatment with cerulenin, a chemical FASN inhibitor, which also downregulated PIP, PIP(2), and PIP(3) but not PI. Thus, dietary fat influences PCa progression and alters phosphoinositides, especially PIP(3), a critical player in the PI3K/AKT pathway. These results may offer appropriate targets, such as FASN, for dietary intervention and/or chemoprevention to reduce PCa incidence and progression.
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spelling pubmed-87067702021-12-30 Altering phosphoinositides in high‐fat diet‐associated prostate tumor xenograft growth Huang, Mingguo Koizumi, Atsushi Narita, Shintaro Nakanishi, Hiroki Sato, Hiromi Kashima, Soki Nara, Taketoshi Kanda, Sohei Numakura, Kazuyuki Saito, Mitsuru Satoh, Shigeru Nanjo, Hiroshi Sasaki, Takehiko Habuchi, Tomonori MedComm (2020) Original Articles The metabolic reprogramming of phospholipids may affect intracellular signal transduction pathways. A high‐fat diet (HFD) is attributed to prostate cancer (PCa) progression, but the expression pattern and role of phospholipids in HFD‐mediated PCa progression remains unclear. In this study, HFD enhanced LNCaP xenograft tumor growth by upregulating the phosphatidylinositol (PI) 3‐kinase (PI3K)/AKT signaling pathway. A lipidomic analysis using xenograft tumors showed that phosphoinositides, especially PI (3,4,5)‐trisphosphate (PIP(3)), including several species containing C38:4, C38:3, and C40:4 fatty acids, increased in the HFD group compared to control. Fatty acid synthase (FASN) was significantly upregulated in xenograft tumors under HFD in both gene and protein levels. PCa cell growth was significantly inhibited through the decreased AKT signaling pathway by treatment with cerulenin, a chemical FASN inhibitor, which also downregulated PIP, PIP(2), and PIP(3) but not PI. Thus, dietary fat influences PCa progression and alters phosphoinositides, especially PIP(3), a critical player in the PI3K/AKT pathway. These results may offer appropriate targets, such as FASN, for dietary intervention and/or chemoprevention to reduce PCa incidence and progression. John Wiley and Sons Inc. 2021-10-28 /pmc/articles/PMC8706770/ /pubmed/34977875 http://dx.doi.org/10.1002/mco2.89 Text en © 2021 The Authors. MedComm published by Sichuan International Medical Exchange & Promotion Association (SCIMEA) and John Wiley & Sons Australia, Ltd. https://creativecommons.org/licenses/by/4.0/This is an open access article under the terms of the http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.
spellingShingle Original Articles
Huang, Mingguo
Koizumi, Atsushi
Narita, Shintaro
Nakanishi, Hiroki
Sato, Hiromi
Kashima, Soki
Nara, Taketoshi
Kanda, Sohei
Numakura, Kazuyuki
Saito, Mitsuru
Satoh, Shigeru
Nanjo, Hiroshi
Sasaki, Takehiko
Habuchi, Tomonori
Altering phosphoinositides in high‐fat diet‐associated prostate tumor xenograft growth
title Altering phosphoinositides in high‐fat diet‐associated prostate tumor xenograft growth
title_full Altering phosphoinositides in high‐fat diet‐associated prostate tumor xenograft growth
title_fullStr Altering phosphoinositides in high‐fat diet‐associated prostate tumor xenograft growth
title_full_unstemmed Altering phosphoinositides in high‐fat diet‐associated prostate tumor xenograft growth
title_short Altering phosphoinositides in high‐fat diet‐associated prostate tumor xenograft growth
title_sort altering phosphoinositides in high‐fat diet‐associated prostate tumor xenograft growth
topic Original Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8706770/
https://www.ncbi.nlm.nih.gov/pubmed/34977875
http://dx.doi.org/10.1002/mco2.89
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