The State Key Laboratory of Bioactive Substance and Function of Natural Medicines, Beijing, 100050, China.
Key Laboratory of Drug Target Research and Drug Screen, Institute of Materia Medica, Chinese Academy of Medical Science and Peking Union Medical College, Beijing, 100050, China.
Acta Pharmacol Sin. 2022 Oct;43(10):2709-2722. doi: 10.1038/s41401-022-00894-7. Epub 2022 Mar 30.
Colorectal cancer (CRC) is the third most common cancer in men and the second most common cancer in women worldwide. CRC is the second leading cause of cancer-related deaths. Although some progress in the treatment of CRC has been achieved, the molecular mechanism of CRC is still unclear. In this study, alcohol dehydrogenase 1C(ADH1C) was first identified as a target gene closely associated with the development of CRC by the comprehensive application of transcriptomics, proteomics, metabonomics and in silico analysis. The ADH1C mRNA and protein expression in CRC cell lines and tumor tissues was lower than that in normal intestinal epithelial cell lines and healthy tissues. Overexpression of ADH1C inhibited the growth, migration, invasion and colony formation of CRC cell lines and prevented the growth of xenograft tumors in nude mice. The inhibitory effects of ADH1C on CRC cells in vitro were exerted by reducing the expression of PHGDH/PSAT1 and the serine level. This inhibition could be partially reversed by adding serine to the culture medium. These results showed that ADH1C is a potential drug target in CRC.
结直肠癌（CRC）是全世界男性中第三常见的癌症，也是女性中第二常见的癌症。CRC 是癌症相关死亡的第二大主要原因。尽管在 CRC 的治疗方面取得了一些进展，但 CRC 的分子机制仍不清楚。在这项研究中，通过综合应用转录组学、蛋白质组学、代谢组学和计算机分析，首次确定醇脱氢酶 1C（ADH1C）是与 CRC 发展密切相关的靶基因。CRC 细胞系和肿瘤组织中的 ADH1C mRNA 和蛋白表达均低于正常肠上皮细胞系和健康组织。ADH1C 的过表达抑制了 CRC 细胞系的生长、迁移、侵袭和集落形成，并阻止了裸鼠异种移植肿瘤的生长。ADH1C 在体外对 CRC 细胞的抑制作用是通过降低 PHGDH/PSAT1 和丝氨酸水平的表达来实现的。在培养基中添加丝氨酸可以部分逆转这种抑制作用。这些结果表明 ADH1C 是 CRC 的一个潜在药物靶点。
