Article

ADH1C inhibits progression of colorectal cancer through the ADH1C/PHGDH /PSAT1/serine metabolic pathway

Sha Li1,2, Hong Yang1,2, Wan Li1,2, Jin-yi Liu1,2, Li-wen Ren1,2, Yi-hui Yang1,2, Bin-bin Ge1,2, Yi-zhi Zhang1,2, Wei-qi Fu1,2, Xiang-jin Zheng1,2, Guan-hua Du1,2, Jin-Hua Wang1,2
1 The State Key Laboratory of Bioactive Substance and Function of Natural Medicines, Beijing 100050, China
2 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
Correspondence to: Guan-hua Du: dugh@imm.ac.cn, Jin-Hua Wang: wjh@imm.ac.cn,
DOI: 10.1038/s41401-022-00894-7
Received: 30 October 2021
Accepted: 27 February 2022
Advance online: 30 March 2022

Abstract

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.
Keywords: colorectal cancer; ADH1C; metabolism; PHGDH; PSAT1; serine

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