<i>N‐</i>glycosylation Modification of CTSD Affects Liver Metastases in Colorectal Cancer
Liver metastasis is the primary factor contributing to unfavorable prognosis in colorectal cancer (CRC). Although N-glycosylation is implicated in metastasis, there is a notable paucity of comprehensive studies addressing the N-glycosylation proteomics associated with liver metastasis in CRC. In this study, N-glycosylated proteins and N-glycosylation sites of differential expression between primary lesions and paired liver metastatic lesions are identified. Cathepsin D (CTSD) is further screened as a potentially pivotal N-glycosylated protein in CRC liver metastasis. Glycosyltransferases complex DDOST and STT3B can regulate N-glycosylation modification at residue 263 of CTSD (a protease), thereby affecting CTSD protease to lyse ACADM. ACADM can regulate ferroptosis-related proteins (ACSL4, SLC7A11, and GPX4) to further influence the invasion and metastasis of CRC cells. This newly discovered mechanism provides potential therapeutic targets for CRC treatment and insights for controlling CRC progression and metastasis.
Authors
- Nan Xiong
- Qin Yan (ORCID: https://orcid.org/0000-0002-3974-0298)
- Long Zhao (ORCID: https://orcid.org/0000-0001-5896-9226)
- Yan Du (ORCID: https://orcid.org/0000-0001-5413-7836)
- Zhanlong Shen (ORCID: https://orcid.org/0000-0002-4277-7067)
- Zhidong Gao (ORCID: https://orcid.org/0000-0002-8415-7587)
- Yingjiang Ye (ORCID: https://orcid.org/0000-0002-7904-3163)
- Jun Zhan (ORCID: https://orcid.org/0000-0001-6904-7999)
- Qing Sun
- Shan Wang (ORCID: https://orcid.org/0000-0003-3314-6455)
- Yan Li (ORCID: https://orcid.org/0000-0002-5838-3185)
- Hongquan Zhang (ORCID: https://orcid.org/0000-0001-8193-0899)
- Caihong Wang (ORCID: https://orcid.org/0000-0003-0817-7946)
- Changjiang Yang
- Chuncui Huang
Institutions
- Chinese Academy of Sciences (CN)
- Peking University (CN)
- Institute of Biophysics (CN)
- Peking University People's Hospital (CN)
- University of Chinese Academy of Sciences (CN)
Publication Details
- Journal
- Advanced Science
- Published
- 2024-12-24
- DOI
- https://doi.org/10.1002/advs.202411740
- Citations
- 11
- Primary Topic
- Glycosylation and Glycoproteins Research
- Type
- article
- Field-Weighted Citation Impact
- 2.57
Funders
- Bethune Charitable Foundation
- Beijing Xisike Clinical Oncology Research Foundation
- National Natural Science Foundation of China
- Natural Science Foundation of Beijing Municipality
- Natural Science Foundation of Chongqing
- Centre Scientifique et Technique du Bâtiment
- National Key Research and Development Program of China