Involvement of Fatty Acid Binding Protein 5 and PPARβ/δin Prostate Cancer Cell Growth

Abstract

Fatty acid binding protein 5 (FABP5) delivers ligands from the cytosol directly to the nuclear receptor PPARβ/δ and thus facilitates the ligation and enhances the transcriptional activity of the receptor. We show here that expression levels of both FABP5 and PPARβ/δ are correlated with the tumorigenic potential of prostate cancer cell lines. We show further that FABP5 comprises a direct target gene for PPARβ/δ and thus the binding protein and its cognate receptor are engaged in a positive feedback loop. The observations demonstrate that, similarly to effects observed in mammary carcinomas, activation of the FABP5/PPARβ/δ pathway induces PPARβ/δ target genes involved in cell survival and growth and enhances cell proliferation and anchorage-independent growth in prostate cancer cells. Furthermore, the data show that downregulation of either FABP5 or PPARβ/δ inhibits the growth of the highly malignant prostate cancer PC3M cells. These studies suggest that the FABP5/PPARβ/δ pathway may play a general role in facilitating tumor progression and that inhibition of the pathway may comprise a novel strategy in treatment of cancer.

High expression of Fatty Acid‐Binding Protein 5 promotes cell growth and metastatic potential of colorectal cancer cells

“…4A,B,F, the FABP5 expression level did not significantly change in response to GW0742 or GSK‐3787, suggesting that FABP5 gene expression is upregulated by a PPAR β/δ‐independent signaling pathway in CRC cells. Thus, these data are contradictory to the report showing that FABP5 is involved in PPAR β/δ‐dependent prostate cancer cell growth 34. Moreover, knockdown of FABP5 expression resulted in the downregulation of fatty acid metabolizing genes, such as acetyl‐CoA carboxylase α (ACCα) and isocitrate dehydrogenase 1 (IDH1) (Fig.…”

Fatty Acid-binding Protein 5 (FABP5) Regulates Cognitive Function Both by Decreasing Anandamide Levels and by Activating the Nuclear Receptor Peroxisome Proliferator-activated Receptor β/δ (PPARβ/δ) in the Brain

“…Among these, FABP5 selectively delivers ligands from the cytosol to the nuclear receptor PPAR␤/␦, and thereby it markedly enhances the transcriptional activity of the receptor (7,8). It was indeed shown that the cooperation between FABP5 and PPAR␤/␦ underlies biological functions such as regulation of energy homeostasis (10) and promotion of prostate and mammary tumorigenesis (11,12). Like FABP5, PPAR␤/␦ is expressed in most regions of the brain (13,14), and it was reported that the FABP5/PPAR␤/␦ pathway inhibits differentiation of a cultured cell model of neuronal stem cells to neuronal progenitor cells, but is necessary for differentiation of progenitor cells to mature neurons (2).…”

Cellular Retinoic Acid-binding Protein 2 Inhibits Tumor Growth by Two Distinct Mechanisms

“…For example, in many carcinoma cells, RAR upregulates genes that trigger differentiation, apoptosis, and cell cycle arrest (12)(13)(14)(15)(16)(17)(18), whereas PPAR␤/␦ induces the expression of genes that promote proliferation, angiogenesis, and survival (3, 19 -22). Consequently, RA inhibits the growth of carcinoma cells that express CRABP2 (11-13, 23, 24) but promotes oncogenic activities in FABP5-expressing cells (3,25,26).…”