Huzhou Key Laboratory of Molecular Medicine, Huzhou Central Hospital, Huzhou Hospital Affiliated with Zhejiang University, Huzhou, Zhejiang 313000, P.R. China.
Huzhou University Schools of Nursing and Medicine, Huzhou University, Huzhou, Zhejiang 313000, P.R. China.
Mol Med Rep. 2022 Aug;26(2). doi: 10.3892/mmr.2022.12784. Epub 2022 Jul 1.
Under aerobic conditions, the preferential use of anaerobic glycolysis by tumour cells leads to a high level of lactate accumulation in tumour microenvironment. Lactate acts not only as a cellular energy source but also as a signalling molecule that regulates cancer cell growth, metastasis and metabolism. It has been reported that a G‑protein‑coupled receptor for lactate named hydroxycarboxylic acid receptor 1 (HCAR1) is highly expressed in numerous types of cancer, but the detailed mechanism remains unclear. In the present study, it was reported that HCAR1 is highly expressed in breast cancer cells. Genetic deletion of in MCF7 cells leads to reduced cell proliferation and migration. Moreover, it was observed that knockout (KO) of attenuated the expression and activity of phosphofructokinase and hexokinase, key rate‑limiting enzymes in glycolysis. Using an extracellular flux analyzer, it was showed that KO of promoted a metabolic shift towards a decreased glycolysis state, as evidenced by a decreased extracellular acidification rate and increased oxygen consumption rate in MCF7 cells. Taken together, our results suggested that lactate acts through HCAR1 as a metabolic regulator in breast cancer cells that may be therapeutically exploited.
在有氧条件下，肿瘤细胞优先利用无氧糖酵解，导致肿瘤微环境中乳酸积累水平升高。乳酸不仅作为细胞能量来源，还作为信号分子调节癌细胞生长、转移和代谢。据报道，一种名为羟基羧酸受体 1（HCAR1）的乳酸 G 蛋白偶联受体在多种类型的癌症中高度表达，但详细机制尚不清楚。在本研究中，报道了 HCAR1 在乳腺癌细胞中高度表达。在 MCF7 细胞中基因敲除 导致细胞增殖和迁移减少。此外，观察到 KO 降低了糖酵解关键限速酶磷酸果糖激酶和己糖激酶的表达和活性。使用细胞外通量分析仪，发现 KO 促进了向降低的糖酵解状态的代谢转变，表现在 MCF7 细胞中，细胞外酸化率降低，耗氧量增加。综上所述，我们的结果表明，乳酸通过 HCAR1 作为代谢调节剂在乳腺癌细胞中发挥作用，这可能具有治疗潜力。
