Department of Pharmaceutical Sciences, College of Pharmacy, Mercer University Health Sciences Center, Mercer University, Atlanta, GA 30341, USA.
Department of Pharmaceutical Sciences, College of Pharmacy, Mercer University Health Sciences Center, Mercer University, Atlanta, GA 30341, USA; Department of Biomedical Sciences, School of Medicine, Mercer University Health Sciences Center, Mercer University, Macon, GA 31207, USA.
Biochem Pharmacol. 2022 Dec;206:115328. doi: 10.1016/j.bcp.2022.115328. Epub 2022 Oct 26.
Globally, breast cancer is the most frequent type of cancer in women, and most breast cancer-associated deaths are due to metastasis and recurrence of the disease. Dietary habits, specifically dietary fat intake is a crucial risk factor involved in breast cancer development and progression. Decades of research has revealed that free-fatty acids (FFA) modulate carcinogenic processes through fatty acid metabolism and lipid peroxidation. The ground-breaking discovery of free-fatty acid receptors, which are members of the G-protein coupled receptor (GPCR) superfamily, has led to the realization that FFA can also act via these receptors to modulate carcinogenic effects. The long-chain free-fatty acid receptors FFA1 (previously termed GPR40) and FFA4 (previously termed GPR120) are activated by mono- and polyunsaturated fatty acids including ω-3, 6, and 9 fatty acids. Initial enthusiasm towards the study of these receptors focused on their insulin secretagogue and sensitization effects, and the downstream associated metabolic regulation. However, recent studies have demonstrated that abnormal expression and/or aberrant FFA1/FFA4 signaling are evident in human breast carcinomas, suggesting that FFA receptors could be a promising target in the treatment of breast cancer. The current review discusses the diverse roles of FFA1 and FFA4 in the regulation of cell proliferation, migration, invasion, and chemotherapy resistance in human breast carcinoma cells and tissue.
在全球范围内，乳腺癌是女性最常见的癌症类型，大多数与乳腺癌相关的死亡是由于疾病的转移和复发。饮食习惯，特别是饮食中的脂肪摄入，是乳腺癌发生和发展的一个关键风险因素。几十年来的研究表明，游离脂肪酸（FFA）通过脂肪酸代谢和脂质过氧化作用来调节致癌过程。游离脂肪酸受体是 G 蛋白偶联受体（GPCR）超家族的成员，这一突破性的发现表明，FFA 也可以通过这些受体来调节致癌作用。长链游离脂肪酸受体 FFA1（以前称为 GPR40）和 FFA4（以前称为 GPR120）被单不饱和脂肪酸和多不饱和脂肪酸（包括 ω-3、6 和 9 脂肪酸）激活。最初对这些受体的研究兴趣集中在它们的胰岛素分泌和敏化作用，以及下游相关的代谢调节上。然而，最近的研究表明，在人类乳腺癌中存在异常表达和/或异常的 FFA1/FFA4 信号，这表明 FFA 受体可能是治疗乳腺癌的一个有前途的靶点。本综述讨论了 FFA1 和 FFA4 在调节人类乳腺癌细胞和组织中的细胞增殖、迁移、侵袭和化疗耐药性方面的不同作用。
