Department of Oncology, The Second Hospital of Lanzhou University, Lanzhou 730030, China.
The Second Clinical Medical College, Lanzhou University, Lanzhou 730030, China.
Acta Biochim Biophys Sin (Shanghai). 2022 May 25;54(5):615-624. doi: 10.3724/abbs.2022038.
Cellular energy metabolism dysregulation is associated with colorectal cancer (CRC) development and progression. Discoidin domain receptor 1a (DDR1a), one of the five DDR1 isoforms, is closely related to cell proliferation, invasion, and apoptosis in various tumors. Whether it participates in cellular metabolic reprogramming and regulates CRC initiation and progression remains unclear. In this study, we compared the expression of DDR1 in CRC tissues and adjacent tissues from 126 postoperative CRC samples. Moreover, lentivirus-mediated DDR1a overexpression and knockdown were performed in LoVo cells, and cell viability and proliferation were determined by CCK-8 and BrdU assays, respectively. Oxygen consumption rate, extracellular acidification rate, and lactate production were used to determine the effect of DDR1a on metabolic reprogramming. Clinically, CRC patients with high DDR1 expression had poor differentiation and were at an advanced TNM stage. DDR1a promoted LoVo cell proliferation, mitochondrial function, and extracellular acidification. Moreover, DDR1a knockdown inhibited intracellular lactic acid production in LoVo cells, while a pyruvate kinase inhibitor (diamide, 200 μM) significantly reversed this progression. Taken together, our results reveal that DDR1 plays a crucial role in maintaining intracellular environment homeostasis through metabolic reprogramming.
细胞能量代谢失调与结直肠癌(CRC)的发生和发展有关。Discoidin domain receptor 1a(DDR1a)是五种 DDR1 亚型之一,与多种肿瘤中的细胞增殖、侵袭和凋亡密切相关。它是否参与细胞代谢重编程以及调节 CRC 的发生和进展尚不清楚。在这项研究中,我们比较了 126 例术后 CRC 样本中 CRC 组织和相邻组织中 DDR1 的表达。此外,我们在 LoVo 细胞中通过慢病毒介导过表达和敲低 DDR1a,分别通过 CCK-8 和 BrdU 测定法测定细胞活力和增殖。通过测定耗氧量、细胞外酸化率和乳酸产量来确定 DDR1a 对代谢重编程的影响。临床上,DDR1 高表达的 CRC 患者分化较差,且处于较晚的 TNM 分期。DDR1a 促进 LoVo 细胞增殖、线粒体功能和细胞外酸化。此外,DDR1a 敲低抑制了 LoVo 细胞中的细胞内乳酸生成,而丙酮酸激酶抑制剂(二酰胺,200 μM)则显著逆转了这一进展。综上所述,我们的研究结果揭示了 DDR1 通过代谢重编程在维持细胞内环境稳态方面发挥着关键作用。