Clinical relevance of gene expression in localized and metastatic prostate cancer exemplified by FABP5

Nitschke, Katja; Erben, Philipp; Waldbillig, Frank; Abdelhadi, A.; Weis, Cleo–Aron; Gottschalt, Maria; Wahby, Sarah; Nuhn, Philipp; Boutros, Michael; Michel, Maurice Stephan; Hardenberg, Jost von; Worst, Thomas

doi:10.1007/s00345-019-02651-8

Cited by 15 publications

(11 citation statements)

References 27 publications

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“…FABP5, however, showed no prognostic significance in this population, suggesting that reported associations of FABP5 with PCa metastasis/progression [46][47][48] may be confounded by other factors such as treatment schemes or cohort composition. A separate study from this one has also shown independence of FABP5 expression from PCa clinical outcomes [49]. reported to be highly expressed in PCa [51], and we have studied and proposed a role for FABP12 in promoting PCa metastasis and progression (discussed below) [29].…”

Section: Introductionmentioning

confidence: 82%

An Amplified Fatty Acid-Binding Protein Gene Cluster in Prostate Cancer: Emerging Roles in Lipid Metabolism and Metastasis

Liu

Godbout

2020

Cancers

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Treatment for early stage and localized prostate cancer (PCa) is highly effective. Patient survival, however, drops dramatically upon metastasis due to drug resistance and cancer recurrence. The molecular mechanisms underlying PCa metastasis are complex and remain unclear. It is therefore crucial to decipher the key genetic alterations and relevant molecular pathways driving PCa metastatic progression so that predictive biomarkers and precise therapeutic targets can be developed. Through PCa cohort analysis, we found that a fatty acid-binding protein (FABP) gene cluster (containing five FABP family members) is preferentially amplified and overexpressed in metastatic PCa. All five FABP genes reside on chromosome 8 at 8q21.13, a chromosomal region frequently amplified in PCa. There is emerging evidence that these FABPs promote metastasis through distinct biological actions and molecular pathways. In this review, we discuss how these FABPs may serve as drivers/promoters for PCa metastatic transformation using patient cohort analysis combined with a review of the literature.

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Section: Introductionmentioning

confidence: 82%

An Amplified Fatty Acid-Binding Protein Gene Cluster in Prostate Cancer: Emerging Roles in Lipid Metabolism and Metastasis

Liu

Godbout

2020

Cancers

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“…FABPs are key intracellular molecules involved in the uptake, transportation and storage of fatty acids and in the mediation of signal transduction and gene transcription [33]. FABP5 promotes various cancer progression and could be correlated to poor prognosis in a wide range of malignant cancers including cervical cancer, breast cancer, prostate cancer and colorectal cancer, et al [34][35][36][37]. Zhao et al [38] indicates that speci c FABP5 silencing reduces the invasiveness and arrest cell cycle in G0/G1 phase, resulting in a signi cant increase in apoptosis of gastric cancer cells.…”

Section: Discussionmentioning

confidence: 99%

FABP5 enhances malignancies of lower-grade gliomas via canonical activation of NF-κB signaling

Wang

Alafate

Wang

et al. 2020

Preprint

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Abstract Background Lower-grade gliomas (LGGs) are grade II/III gliomas based on the WHO classification with significant genetic heterogeneity and clinical properties. Traditional histological classification of gliomas has been challenged by the improvement of molecular stratification, however, the reproducibility and diagnostic accuracy of LGGs classification remain poor. Methods In this study, we derived all relevant data of LGGs including TCGA and CGGA databases from official websites. Bioinformatic analyses unveiled the clinical significance of FABP5 and its potential downstream targets. IHC, qRT-PCR and western blot assays were further conducted to validate those bioinformatic findings. Moreover, lentiviral transduction assays were performed to evaluate the function of FABP5 in patient-derived cell lines. Results We identified fatty acid binding protein 5 (FABP5) as one of the most enriched genes in malignant LGGs and elevated FABP5 revealed severe outcomes in LGGs. Functionally, lentiviral suppression of FABP5 reduced malignant characters including proliferation, cloning formation, migration, invasion and TMZ resistance, contrarily, the malignancies of LGGs were enhanced by exogenous overexpression of FABP5. Mechanistically, epithelial-mesenchymal transition (EMT) was correlated to FABP5 expression in LGGs and tumor necrosis factor α (TNFα)-dependent NF-κB signaling was involved in this process. Furthermore, FABP5 induced phosphorylation of inhibitor of nuclear factor kappa-B kinase α (IKKα) thus activated nuclear factor kappa-B (NF-κB) signaling. Conclusion Taken together, our study indicated that FABP5 enhances malignancies of LGGs through canonical activation of NF-κB signaling, which could be used as individualized prognostic biomarker and potential therapeutic target of LGGs.

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“…FABP5 is the most characterized and highly expressed FABP in human PCas and cell lines, especially in CRPC cells (81)(82)(83)(84)(85)(86)(87)(88). Different mechanisms account for FABP5 upregulation, including a positive feedback loop mediated by include proliferator-activated receptors (PPAR) PPARb/d (89), CpG island hypomethylation (85), and gene amplification (90).…”

Section: Alterations In Fa Transportmentioning

confidence: 99%

“…Different mechanisms account for FABP5 upregulation, including a positive feedback loop mediated by include proliferator-activated receptors (PPAR) PPARβ/δ ( 89 ), CpG island hypomethylation ( 85 ), and gene amplification ( 90 ). The latter is highly frequent in advanced CRPC ( 88 ). In human PCas, a positive correlation between FABP5 expression and androgen signaling responsive genes was observed.…”

Section: Lipid Metabolism Rewiring In Pca Development and Progressionmentioning

confidence: 99%

Prostate Cancer Progression: as a Matter of Fats

2021

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Advanced prostate cancer (PCa) represents the fifth cause of cancer death worldwide. Although survival has improved with second-generation androgen signaling and Parp inhibitors, the benefits are not long-lasting, and new therapeutic approaches are sorely needed. Lipids and their metabolism have recently reached the spotlight with accumulating evidence for their role as promoters of PCa development, progression, and metastasis. As a result, interest in targeting enzymes/transporters involved in lipid metabolism is rapidly growing. Moreover, the use of lipogenic signatures to predict prognosis and resistance to therapy has been recently explored with promising results. Despite the well-known association between obesity with PCa lethality, the underlying mechanistic role of diet/obesity-derived metabolites has only lately been unveiled. Furthermore, the role of lipids as energy source, building blocks, and signaling molecules in cancer cells has now been revisited and expanded in the context of the tumor microenvironment (TME), which is heavily influenced by the external environment and nutrient availability. Here, we describe how lipids, their enzymes, transporters, and modulators can promote PCa development and progression, and we emphasize the role of lipids in shaping TME. In a therapeutic perspective, we describe the ongoing efforts in targeting lipogenic hubs. Finally, we highlight studies supporting dietary modulation in the adjuvant setting with the purpose of achieving greater efficacy of the standard of care and of synthetic lethality. PCa progression is “a matter of fats”, and the more we understand about the role of lipids as key players in this process, the better we can develop approaches to counteract their tumor promoter activity while preserving their beneficial properties.

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Clinical relevance of gene expression in localized and metastatic prostate cancer exemplified by FABP5

Cited by 15 publications

References 27 publications

An Amplified Fatty Acid-Binding Protein Gene Cluster in Prostate Cancer: Emerging Roles in Lipid Metabolism and Metastasis

An Amplified Fatty Acid-Binding Protein Gene Cluster in Prostate Cancer: Emerging Roles in Lipid Metabolism and Metastasis

FABP5 enhances malignancies of lower-grade gliomas via canonical activation of NF-κB signaling

Prostate Cancer Progression: as a Matter of Fats

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