# Fatty Acid Metabolism Regulators Have Pivotal Roles in the Pathogenesis of Ovarian Carcinoma

**Authors:** Megumi Watanabe, Motoki Matsuura, Tatsuya Sato, Makoto Usami, Tsuyoshi Saito, Masato Furuhashi, Kohichi Takada, Hiroshi Ohguro

PMC · DOI: 10.3390/ijms26104794 · International Journal of Molecular Sciences · 2025-05-16

## TL;DR

This study shows that fatty acid metabolism regulators play a key role in ovarian cancer development and could help predict patient outcomes.

## Contribution

The study identifies fatty acid metabolism regulators as novel prognostic factors for ovarian serous adenocarcinoma.

## Key findings

- AMOC-2 and ES2 ovarian cancer cells form non-globe-shaped spheroids with distinct metabolic profiles compared to non-cancerous cells.
- FABP4, FABP5, and PPARγ are overexpressed in AMOC-2 cells compared to healthy ovarian cells.
- Multiomic analysis links these regulators to prognosis prediction in ovarian serous adenocarcinoma.

## Abstract

To study the pathological contribution of fatty acid (FA) metabolism regulators including fatty acid binding protein 4 (FABP4), FABP5, peroxisome proliferator-activated receptor alpha (PPARα), and PPARγ in ovarian carcinoma, non-cancerous human ovarian surface epithelium (HOSE) cells and two epithelial ovarian carcinoma (EOC) cell lines, AMOC-2 and ES2 established from ovarian serous adenocarcinoma and ovarian clear cell carcinoma, respectively, were subjected to (1) an analysis of the physical properties of spheroids, (2) qPCR analysis, (3) cellular metabolic analysis, and (4) multiomic pan-cancer analysis using the Cancer Genome Atlas (TCGA). In contrast to globe-shaped spheroids of HOSE cells, AMOC-2 and ES2 cells formed non-globe-shaped spheroids and ES2 spheroids were much more fragile than AMOC-2 spheroids. Gene expression levels of FABP4 and FABP5 in AMOC-2 cells and those of PPARγ in AMOC-2 cells were significantly higher than those in HOSE cells. Metabolic phenotypes and the effectiveness against antagonists for regulators were significantly different in the two types of cancerous cells. Those regulators were identified by a multiomic pan-cancer analysis as novel factors for the prediction of the prognosis of ovarian serous adenocarcinoma. The results show that dysregulated FA metabolism in AMOC-2 and ES2 suggests that the regulation of FA metabolism may be a critical factor in the pathogenesis of EOC.

## Linked entities

- **Genes:** FABP4 (fatty acid binding protein 4) [NCBI Gene 2167], FABP5 (fatty acid binding protein 5) [NCBI Gene 2171], PPARA (peroxisome proliferator activated receptor alpha) [NCBI Gene 5465], PPARG (peroxisome proliferator activated receptor gamma) [NCBI Gene 5468]
- **Diseases:** ovarian carcinoma (MONDO:0005140), ovarian serous adenocarcinoma (MONDO:0005211)
- **Species:** Homo sapiens (taxon 9606)

## Full-text entities

- **Genes:** FABP4 (fatty acid binding protein 4) [NCBI Gene 2167] {aka A-FABP, AFABP, ALBP, HEL-S-104, aP2}, PPARG (peroxisome proliferator activated receptor gamma) [NCBI Gene 5468] {aka CIMT1, FPLD3, GLM1, NR1C3, PPARG1, PPARG2}, PPARA (peroxisome proliferator activated receptor alpha) [NCBI Gene 5465] {aka NR1C1, PPAR, PPAR-alpha, PPARalpha, hPPAR}, FABP5 (fatty acid binding protein 5) [NCBI Gene 2171] {aka E-FABP, EFABP, KFABP, PA-FABP, PAFABP}
- **Diseases:** Cancer (MESH:D009369), ovarian surface (MESH:D010049), Ovarian Carcinoma (MESH:D010051), EOC (MESH:D000077216)
- **Chemicals:** FA (MESH:D005227)
- **Species:** Homo sapiens (human, species) [taxon 9606]
- **Cell lines:** AMOC-2 — Homo sapiens (Human), Ovarian serous adenocarcinoma, Cancer cell line (CVCL_C830), ES2 — Homo sapiens (Human), Embryonic stem cell (CVCL_C769), HOSE — Rattus norvegicus (Rat), Spontaneously immortalized cell line (CVCL_B6GZ)

## Full text

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## Figures

8 figures with captions in the complete paper: https://tomesphere.com/paper/PMC12112331/full.md

## References

70 references — full list in the complete paper: https://tomesphere.com/paper/PMC12112331/full.md

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Source: https://tomesphere.com/paper/PMC12112331