Chinese Researchers Uncover Key Role of DNA Repair Protein Lactylation in Tumor Chemotherapy Resistance
TapTechNews July 6th news, the team of Professors He Yulong and Zhang Changhua from the Seventh Affiliated Hospital of Sun Yat-sen University published a paper in the journal Nature on July 3rd, uncovering the key regulatory role of lactylation of a DNA repair protein (NBS1) protein in tumor chemotherapy resistance, solving the century-old mystery of tumor sugar metabolism and drug resistance mechanism.
The title of the paper is NBS1 lactylation is required for efficient DNA repair and chemotherapy resistance, and it proposes a new strategy of reversing drug resistance by inhibiting this modification or regulating lactic acid metabolism.
Professor Zhang Changhua said:
The research not only reveals how tumor cells resist chemotherapy through sugar metabolism, but also screens out a targeted drug that can effectively block the generation of drug resistance in tumor cells, which will have a profound impact on tumor diagnosis and treatment.
The research also opens up a new perspective for the study of tumor immunotherapy, tumor recurrence and metastasis and other issues, and is expected to break through the bottleneck of tumor chemotherapy resistance treatment.
Scientists have raised questions as early as more than 100 years ago, why tumor cells have such strong self-repair and adaptability? How to crack the drug resistance mechanism of tumor cells?
No matter in aerobic or anaerobic environment, tumor cells, different from normal cells, will metabolize through the glycolysis pathway and produce a large amount of lactic acid.
But for hundreds of years, the medical community has been unable to clearly explain why tumor cells use this high consumption and low energy production method for metabolism.
Our research team spent more than 4 years, through proteomics, metabolomics and lactylation modification omics to carry out experimental demonstrations. By analyzing the specimens of gastric tumor tissues that are sensitive or resistant to neoadjuvant chemotherapy, it is found that in the drug-resistant tumor tissues, the glycolysis pathway is significantly up-regulated and the lactic acid level is significantly increased.
The team of Professors He Yulong and Zhang Changhua found through a large number of experiments that lactic acid plays a key role in DNA repair and chemotherapy resistance, equivalent to the resurrection armor of tumor cells, so they further studied it and clarified the influence of lactylation modification of DNA repair protein (NBS1) protein in the tumor drug resistance mechanism.
The Warburg effect is an important metabolic characteristic of tumor cells. The reason why the growth rate of cancer cells is much greater than that of normal cells is the difference in the source of energy: tumor cells tend to generate energy through the glycolysis pathway, while he althy cells mainly rely on mitochondrial oxidative phosphorylation to generate energy.
The research results show that lactic acid in tumor cells can enhance the DNA damage repair ability of tumor cells by promoting the lactylation process. When tumor cells are damaged by radiotherapy and chemotherapy, they can quickly repair the damaged DNA, thereby reducing the effect of radiotherapy and chemotherapy and leading to the occurrence of drug resistance.
TapTechNews attached the reference address