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Phospholipase Cɛ Regulates Prostate Cancer Lipid Metabolism and Proliferation by Targeting AMP-Activated Protein Kinase (AMPK)/Sterol Regulatory Element-Binding Protein 1 (SREBP-1) Signaling Pathway
BACKGROUND: Metabolic reprogramming is a common characteristic of numerous kinds of tumors, including prostate cancer (PCa). Tumor metabolism such as lipid metabolism provides sufficient lipids for tumor cell division and rapid growing as well as a vital source for formation of new cellular membrane...
Autores principales: | , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
International Scientific Literature, Inc.
2020
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7392057/ https://www.ncbi.nlm.nih.gov/pubmed/32696762 http://dx.doi.org/10.12659/MSM.924328 |
Sumario: | BACKGROUND: Metabolic reprogramming is a common characteristic of numerous kinds of tumors, including prostate cancer (PCa). Tumor metabolism such as lipid metabolism provides sufficient lipids for tumor cell division and rapid growing as well as a vital source for formation of new cellular membranes. Phospholipase Cɛ (PLCɛ) is an oncogene that can drive proliferation, progression, and lipid metabolism of tumors, but its effect in lipid metabolism of PCa is not clear. MATERIAL/METHODS: Benign prostatic hyperplasia (BPH) and PCa tissue specimens were assessed for SREBP-1, FASN, and PLCɛ by immunohistochemistry, and PLCɛ was knocked-down by a lentiviral short hairpin RNA. The mRNA and protein level expression of related factors were tested by qPCR and Western blot analyses. Cell proliferation was assessed by clone formation, CCK-8, and Ki-67 assays. Nile red and oil red O staining were performed to detect endogenous lipid levels. Immunofluorescence was used to localize the protein of SREBP-1. Finally, a tumor xenograft assay of nude mice was performed to assess the role of PLCɛ in prostate tumor generation. RESULTS: We found that overexpression of PLCɛ indicates low PFS in PCa and is involved in metastasis of PCa, and that the PLCɛ/AMPK/SREBP-1 signaling network promotes the progression of PCa through lipid metabolism in vivo and in vitro. CONCLUSIONS: This study is the first to discover the lethal role of PLCɛ in lipid metabolism and malignant behavior of PCa, elucidation PCa occurrence and progression. |
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