Laboratory of Xenobiotic Metabolism and Environmental Toxicology, Faculty of Pharmaceutical Sciences, Hiroshima International University (HIU), 5-1-1 Hiro-koshingai, Kure, Hiroshima, 737-0112, Japan.
Labaratory of Hygienic Chemistry, Daiichi University of Pharmacy, 22-1 Tamagawa-cho, Minami-ku, Fukuoka, 815-8511, Japan.
Biochem Biophys Res Commun. 2020 Oct 15;531(2):215-222. doi: 10.1016/j.bbrc.2020.07.043. Epub 2020 Aug 11.
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.
脂肪酸 2-羟化酶（FA2H）的功能作用在癌症生物学领域存在争议，这是由于 FA2H 的双重作用，特别是与其与三阴性乳腺癌（TNBC）的相互作用有关。之前的一项生物化学和临床重点研究表明，FA2H 可能会抑制 TNBC 的侵袭性。然而，另一项流行病学研究表明，FA2H 的表达与 TNBC 病例无病生存时间缩短有关。我们报道 FA2H 是人类乳腺癌 MDA-MB-231 细胞中过氧化物酶体增殖物激活受体 α（PPARα）调节的基因，是 TNBC 分析的体外实验模型。其配体激活 PPARα 据报道会导致 MDA-MB-231 细胞表现出侵袭性，以及雌激素受体 α（ERα）阳性 MCF-7 细胞。这项研究的结果表明：i）与 MCF-7 细胞相比，MDA-MB-231 细胞表达的 FA2H 水平非常低，这反映了与 MCF-7 细胞相比，FA2H 的基础水平 PPARα 驱动的转录活性较低，ii）增加的 FA2H 表达刺激 MDA-MB-231 和 MCF-7 乳腺癌细胞迁移，而不影响增殖。总之，我们的发现表明，FA2H 可能是一种乳腺癌细胞迁移刺激物，与 ERα 表达状态无关。
