Nucleolin malonylation as a nuclear-cytosol signal exchange mechanism to drive cell proliferation in Hepatocarcinoma by enhancing AKT translation
Cancer cells undergo metabolic reprogramming that is intricately linked to malignancy. Protein acylations are especially responsive to metabolic changes, influencing signal transduction pathways and fostering cell proliferation. However, as a novel type of acylations, the involvement of malonylation in cancer remains poorly understood. In this study, we observed a significant reduction in malonyl-CoA levels in hepatocellular carcinoma (HCC), which correlated with a global decrease in malonylation. Subsequent nuclear malonylome analysis unveiled nucleolin (NCL) malonylation, which was notably enhanced in HCC biopsies. we demonstrated that NCL undergoes malonylation at lysine residues 124 and 398. This modification triggers the translocation of NCL from the nucleolus to nucleoplasm and cytoplasm, binding to AKT mRNA, and promoting AKT translation in HCC. Silencing AKT expression markedly attenuated HCC cell proliferation driven by NCL malonylation. These findings collectively highlight nuclear signaling in modulating AKT expression, suggesting NCL malonylation as a novel mechanism through which cancer cells drive cell proliferation.
Authors
- Hao Cui (ORCID: https://orcid.org/0000-0001-8804-0629)
- Keli Chai
- Junnian Zheng (ORCID: https://orcid.org/0000-0002-3794-6356)
- Zhongjun Zhao (ORCID: https://orcid.org/0000-0001-8346-0421)
- Jiehui Di
- Qiong Zhao (ORCID: https://orcid.org/0000-0002-0011-2980)
- Guanghou Shui (ORCID: https://orcid.org/0000-0002-1621-9643)
- Tao Liu (ORCID: https://orcid.org/0000-0001-6244-7316)
- Yang Sun (ORCID: https://orcid.org/0000-0001-5669-4134)
- Xuefei Zhong
- Yong Liu (ORCID: https://orcid.org/0000-0002-0574-2877)
- Yuting Qian (ORCID: https://orcid.org/0000-0003-2342-4001)
- Yang Tian (ORCID: https://orcid.org/0000-0003-1013-390X)
- Lianjun Zhang (ORCID: https://orcid.org/0000-0003-3151-9764)
- Bao Zhu (ORCID: https://orcid.org/0000-0001-8195-1665)
- Hanjing Meng
- Shutao Guo
- Mingyi Xia
- Liang Sun (ORCID: https://orcid.org/0000-0002-0034-2567)
Institutions
- Jiangsu University (CN)
- Xuzhou Medical College (CN)
- Chinese Academy of Sciences (CN)
- Chinese Academy of Medical Sciences & Peking Union Medical College (CN)
- Nankai University (CN)
- Xuzhou Cancer Hospital (CN)
- Ingenierie des Materiaux polymeres (FR)
- Suzhou Institute of Systems Medicine (CN)
- Institute of Genetics and Developmental Biology (CN)
Publication Details
- Journal
- Journal of Biological Chemistry
- Published
- 2024-09-19
- DOI
- https://doi.org/10.1016/j.jbc.2024.107785
- Citations
- 10
- Primary Topic
- Sirtuins and Resveratrol in Medicine
- Type
- article
- Field-Weighted Citation Impact
- 3.44
Funders
- National Natural Science Foundation of China