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

Autor: Mingguo Huang, Atsushi Koizumi, Shintaro Narita, Hiroki Nakanishi, Hiromi Sato, Soki Kashima, Taketoshi Nara, Sohei Kanda, Kazuyuki Numakura, Mitsuru Saito, Shigeru Satoh, Hiroshi Nanjo, Takehiko Sasaki, Tomonori Habuchi
Jazyk: angličtina
Rok vydání: 2021
Předmět:
Zdroj: MedComm, Vol 2, Iss 4, Pp 756-764 (2021)
Druh dokumentu: article
ISSN: 2688-2663
DOI: 10.1002/mco2.89
Popis: Abstract 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 (PIP3), 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, PIP2, and PIP3 but not PI. Thus, dietary fat influences PCa progression and alters phosphoinositides, especially PIP3, 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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