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.
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25 June 2024
A Correction to this paper has been published: https://doi.org/10.1038/s41401-024-01319-3
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Acknowledgements
This research was funded by Beijing Natural Science Foundation (7212157), CAMS Innovation Fund for Medical Sciences (2021-1-I2M-029), National Natural Science Foundation of China (81803584, 81703536), Technology Major Projects for “Major New Drugs Innovation and Development” (2018ZX09711001-005-025, 2018ZX09711001-012), National Natural Science Foundation of China (82073311).
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JHW and GHD developed the hypothesis, designed the experiments, and revised the manuscript. SL conducted most experiments and wrote the main manuscript. HY, JYL and LWR accomplished the rest experiments, WL, YHY, BBG, YZZ, WQF and XJZ collected data and performed the statistical analysis. All authors read and approved the final manuscript.
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The original online version of this article was revised: errors in the previously published images of Fig. 6d, e and Suppl Fig. 8c,d. These inaccuracies were due to an oversight during the preparation of the figures.
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Li, S., Yang, H., Li, W. et al. ADH1C inhibits progression of colorectal cancer through the ADH1C/PHGDH /PSAT1/serine metabolic pathway. Acta Pharmacol Sin 43, 2709–2722 (2022). https://doi.org/10.1038/s41401-022-00894-7
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