Fatty acid 2-hydroxylase (FA2H) as a stimulatory molecule responsible for breast cancer cell migration

脂肪酸 2-羟化酶 (FA2H) 是促进乳腺癌细胞迁移的刺激分子

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作者:Masayo Hirao-Suzuki, Takayuki Koga, Genki Sakai, Takanobu Kobayashi, Yuji Ishii, Hiroshi Miyazawa, Masufumi Takiguchi, Narumi Sugihara, Akihisa Toda, Masahiro Ohara, Shuso Takeda

Abstract

The functional role of fatty acid 2-hydroxylase (FA2H) is controversial in the field of cancer biology due to the dual role of FA2H, particularly related to its interaction with triple-negative breast cancer (TNBC). A previous biochemical- and clinical-focused study suggested that FA2H could dampen TNBC aggressiveness. However, another epidemiological study demonstrated that FA2H expression is associated with shorter disease-free survival in TNBC cases. We reported that FA2H is a peroxisome proliferator-activated receptor α (PPARα)-regulated gene in human breast cancer MDA-MB-231 cells, in vitro experimental models for TNBC analysis. PPARα activation by its ligand reportedly results in an aggressive MDA-MB-231 cell phenotype, as well as estrogen receptor α (ERα)-positive MCF-7 cells. The results of this study show that i) MDA-MB-231 cells express very low levels of FA2H compared to the MCF-7 cells, reflecting a low basal-level PPARα-driven transcriptional activity compared to the MCF-7 cells, and ii) the increased FA2H expression stimulates the MDA-MB-231 and MCF-7 breast cancer cell migration without affecting proliferation. Taken together, our findings indicate that FA2H might be a breast cancer cell migration stimulator, independently of the ERα expression status.

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