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journal article·2025-02Open access

N‐glycosylation Modification of CTSD Affects Liver Metastases in Colorectal Cancer

Nan Xiong, Yan Du, Chuncui Huang, Quanyi Yan, Long Zhao, Changjiang Yang, Qing Sun, Zhidong Gao, Caihong Wang, Jun Zhan, Hongquan Zhang, Shan Wang, Yingjiang Ye, Yan Li, Zhanlong Shen

Advanced Science· Volume 12· Issue 7
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Source abstract

Abstract

Abstract 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.
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Research context

OpenAlex topics: Glycosylation and Glycoproteins Research · Galectins and Cancer Biology · RNA modifications and cancer

SciVX discovery tags are terminology-based. OpenAlex topics are source-provided classifications.

Affiliations

Department of Gastroenterological Surgery Peking University People's Hospital Beijing 100044 China

Beijing Key Laboratory of Colorectal Cancer Diagnosis and Treatment Research Beijing 100044 China

Laboratory of Surgical Oncology Peking University People's Hospital Beijing 100044 China

Key Laboratory of Epigenetic Regulation and Intervention Institute of Biophysics Chinese Academy of Sciences 15 Datun Road Beijing 100101 China

University of Chinese Academy of Sciences 19 Yuquan Road Beijing 100049 China

Western Institute of Health Data Science 28 High Tech Avenue Chongqing 401329 China

Program for Cancer and Cell Biology Department of Human Anatomy Histology and Embryology School of Basic Medical Sciences Peking University Health Science Center Beijing 100191 China

Funding

National Natural Science Foundation of China · Natural Science Foundation of Beijing Municipality · Beijing Xisike Clinical Oncology Research Foundation · National Key Research and Development Program of China

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