Dysfunctional Lipid Metabolism—The Basis for How Genetic Abnormalities Express the Phenotype of Aggressive Prostate Cancer

Alberto, Matthew; Yim, Arthur; Lawrentschuk, Nathan; Bolton, Damien

doi:10.3390/cancers15020341

Cited by 3 publications

(2 citation statements)

References 54 publications

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“…From pathway enrichment, PF-L metabolites potentially regulate the AMPK signaling pathway, EGFR tyrosine kinase inhibitor resistance, miRNAs in cancer, prostate cancer, steroid and lipid metabolism, SCF-KIT and PIK3/Akt signaling pathways, EPH-ephrin mediated cell repulsion, and the VEGFA-VEGFR2 pathway. Collectively, these pathways were discovered to significantly affect the tumorigenesis, growth, progression, energy regulation, metastasis, and adhesion of PCa cells [ 61 , 62 , 63 , 64 , 65 , 66 , 67 , 68 , 69 ].…”

Section: Discussionmentioning

confidence: 99%

An In Vitro Evaluation and Network Pharmacology Analysis of Prospective Anti-Prostate Cancer Activity from Perilla frutescens

Garcia,

Huang,

De Castro-Cruz

et al. 2023

Plants

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Perilla frutescens (L.) Britt. is extensively cultivated in East Asia as a dietary vegetable, and nutraceuticals are reportedly rich in bioactive compounds, especially with anticancer activities. This study explored the in vitro cytotoxic effects of P. frutescens parts’ (stems, leaves, and seeds) extracts on prostate cancer cells (DU-145) and possible interactions of putative metabolites to related prostate cancer targets in silico. The ethanol extract of P. frutescens leaves was the most cytotoxic for the prostate cancer cells. From high-performance liquid chromatography analysis, rosmarinic acid was identified as the major metabolite in the leaf extracts. Network analysis revealed interactions from multiple affected targets and pathways of the metabolites. From gene ontology enrichment analysis, P. frutescens leaf metabolites could significantly affect 14 molecular functions and 12 biological processes in five cellular components. Four (4) KEGG pathways, including for prostate cancer, and six (6) Reactome pathways were shown to be significantly affected. The molecular simulation confirmed the interactions of relevant protein targets with key metabolites, including rosmarinic acid. This study could potentially lead to further exploration of P. frutescens leaves or their metabolites for prostate cancer treatment and prevention.

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Section: Discussionmentioning

confidence: 99%

An In Vitro Evaluation and Network Pharmacology Analysis of Prospective Anti-Prostate Cancer Activity from Perilla frutescens

Garcia,

Huang,

De Castro-Cruz

et al. 2023

Plants

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“…Reprogramming of fatty acid signaling and metabolic pathways accompanies the progression of PC [29,30]. FABP5 is the principal FABP that is upregulated in advanced PC and is implicated as a critical driver of PC metastasis [5][6][7][8].…”

Section: Discussionmentioning

confidence: 99%

Fatty acid binding protein 5 regulates docetaxel sensitivity in taxane-resistant prostate cancer cells

Hillowe,

Gordon,

Wang

et al. 2023

PLoS ONE

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Prostate cancer is a leading cause of cancer-related deaths in men in the United States. Although treatable when detected early, prostate cancer commonly transitions to an aggressive castration-resistant metastatic state. While taxane chemotherapeutics such as docetaxel are mainstay treatment options for prostate cancer, taxane resistance often develops. Fatty acid binding protein 5 (FABP5) is an intracellular lipid chaperone that is upregulated in advanced prostate cancer and is implicated as a key driver of its progression. The recent demonstration that FABP5 inhibitors produce synergistic inhibition of tumor growth when combined with taxane chemotherapeutics highlights the possibility that FABP5 may regulate other features of taxane function, including resistance. Employing taxane-resistant DU145-TXR cells and a combination of cytotoxicity, apoptosis, and cell cycle assays, our findings demonstrate that FABP5 knockdown sensitizes the cells to docetaxel. In contrast, docetaxel potency was unaffected by FABP5 knockdown in taxane-sensitive DU145 cells. Taxane-resistance in DU145-TXR cells stems from upregulation of the P-glycoprotein ATP binding cassette subfamily B member 1 (ABCB1). Expression analyses and functional assays confirmed that FABP5 knockdown in DU145-TXR cells markedly reduced ABCB1 expression and activity, respectively. Our study demonstrates a potential new function for FABP5 in regulating taxane sensitivity and the expression of a major P-glycoprotein efflux pump in prostate cancer cells.

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Characterization of metabolism-associated molecular patterns in prostate cancer

et al. 2023

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Background Metabolism is a hallmark of cancer and it involves in resistance to antitumor treatment. Therefore, the purposes of this study are to classify metabolism-related molecular pattern and to explore the molecular and tumor microenvironment characteristics for prognosis predicting in prostate cancer. Methods The mRNA expression profiles and the corresponding clinical information for prostate cancer patients from TCGA, cBioPortal, and GEO databases. Samples were classified using unsupervised non-negative matrix factorization (NMF) clustering based on differentially expressed metabolism-related genes (MAGs). The characteristics of disease-free survival (DFS), clinicopathological characteristics, pathways, TME, immune cell infiltration, response to immunotherapy, and sensitivity to chemotherapy between subclusters were explored. A prognostic signature was constructed by LASSO cox regression analysis based on differentially expressed MAGs and followed by the development for prognostic prediction. Results A total of 76 MAGs between prostate cancer samples and non-tumorous samples were found, then 489 patients were divided into two metabolism-related subclusters for prostate cancer. The significant differences in clinical characteristics (age, T/N stage, Gleason) and DFS between two subclusters. Cluster 1 was associated with cell cycle and metabolism-related pathways, and epithelial-mesenchymal transition (EMT), etc., involved in cluster 2. Moreover, lower ESTIMATE/immune/stromal scores, lower expression of HLAs and immune checkpoint-related genes, and lower half-maximal inhibitory concentration (IC50) values in cluster 1 compared with cluster 2. The 10 MAG signature was identified and constructed a risk model for DFS predicting. The patients with high-risk scores showed poorer DFS. The area under the curve (AUC) values for 1-, 3-, 5-year DFS were 0.744, 0.731, 0.735 in TCGA-PRAD dataset, and 0.668, 0.712, 0.809 in GSE70768 dataset, 0.763, 0.802, 0.772 in GSE70769 dataset. Besides, risk score and Gleason score were identified as independent factors for DFS predicting, and the AUC values of risk score and Gleason score were respectively 0.743 and 0.738. The nomogram showed a favorable performance in DFS predicting. Conclusion Our data identified two metabolism-related molecular subclusters for prostate cancer that were distinctly characterized in prostate cancer. Metabolism-related risk profiles were also constructed for prognostic prediction.

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Dysfunctional Lipid Metabolism—The Basis for How Genetic Abnormalities Express the Phenotype of Aggressive Prostate Cancer

Cited by 3 publications

References 54 publications

An In Vitro Evaluation and Network Pharmacology Analysis of Prospective Anti-Prostate Cancer Activity from Perilla frutescens

An In Vitro Evaluation and Network Pharmacology Analysis of Prospective Anti-Prostate Cancer Activity from Perilla frutescens

Fatty acid binding protein 5 regulates docetaxel sensitivity in taxane-resistant prostate cancer cells

Characterization of metabolism-associated molecular patterns in prostate cancer

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