Oncotarget

Research Papers:

A novel fatty acid-binding protein 5-estrogen-related receptor α signaling pathway promotes cell growth and energy metabolism in prostate cancer cells

Shogo Senga, Koichiro Kawaguchi, Narumi Kobayashi, Akira Ando and Hiroshi Fujii _

PDF  |  HTML  |  Supplementary Files  |  How to cite  |  Order a Reprint

Oncotarget. 2018; 9:31753-31770. https://doi.org/10.18632/oncotarget.25878

Metrics: PDF 816 views  |   HTML 2891 views  |   ?  


Abstract

Shogo Senga1, Koichiro Kawaguchi1, Narumi Kobayashi2, Akira Ando2 and Hiroshi Fujii3

1Interdisciplinary Graduate School of Science and Technology, Shinshu University, Minami-minowa, Kami-ina, Nagano, 399-4598, Japan

2Department of Biomedical Engineering, Graduate School of Science and Technology, Shinshu University, Minami-minowa, Kami-ina, Nagano, 399-4598, Japan

3Department of Interdisciplinary Genome Sciences and Cell Metabolism, Institute for Biomedical Sciences, Interdisciplinary Cluster for Cutting-Edge Research, Shinshu University, Minami-minowa, Kami-ina, Nagano, 399-4598, Japan

Correspondence to:

Hiroshi Fujii, email: hfujii@shinshu-u.ac.jp

Keywords: FABP5; ERRα; PGC-1β; energy metabolism; prostate cancer

Received: February 13, 2018     Accepted: July 21, 2018     Published: August 03, 2018

ABSTRACT

Epidermal or cutaneous fatty acid-binding protein is an intracellular lipid-binding protein, also known as FABP5, and its expression level is closely related to cancer cell proliferation and metastatic activities in various types of carcinoma. However, the molecular mechanisms of FABP5 in cancer cell proliferation and its other functions have remained unclear. In the present study, we have clearly revealed that FABP5 activated expression of metabolic genes (ATP5B, LCHAD, ACO2, FH and MFN2) via a novel signaling pathway in an ERRα (estrogen-related receptor α)-dependent manner in prostate cancer cell lines. To clarify the novel function of FABP5, we examined the activation mechanisms of the ERRα target genes via FABP5. A direct protein-protein interaction between FABP5 and ERRα was demonstrated by immunoprecipitation and GST pull-down assays. We have clearly revealed that FABP5 interacted directly with transcriptional complex containing ERRα and its co-activator PGC-1β to increase expression of the ERRα target genes. In addition, we have shown that FABP5 knockdown induced high energy stress leading to induction of apoptosis and cell cycle arrest via AMPK-FOXO3A signaling pathway in prostate cancer cells, suggesting that FABP5 plays an important role in cellular energy status directing metabolic adaptation to support cellular proliferation and survival.


Creative Commons License All site content, except where otherwise noted, is licensed under a Creative Commons Attribution 3.0 License.
PII: 25878