2. Academic Validation
  3. N-glycosylation Modification of CTSD Affects Liver Metastases in Colorectal Cancer

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

  • Adv Sci (Weinh). 2024 Dec 24:e2411740. doi: 10.1002/advs.202411740.
Nan Xiong 1 2 3,  Yan Du 1 2 3,  Chuncui Huang 4 5,  Quanyi Yan 6,  Long Zhao 1 2 3,  Changjiang Yang 1 2 3,  Qing Sun 4 5,  Zhidong Gao 1 2 3,  Caihong Wang 1 2 3,  Jun Zhan 7,  Hongquan Zhang 7,  Shan Wang 1 2 3,  Yingjiang Ye 1 2 3,  Yan Li 4 5,  Zhanlong Shen 1 2 3
Affiliations

Affiliations

  • 1 Department of Gastroenterological Surgery, Peking University People's Hospital, Beijing, 100044, China.
  • 2 Beijing Key Laboratory of Colorectal Cancer Diagnosis and Treatment Research, Beijing, 100044, China.
  • 3 Laboratory of Surgical Oncology, Peking University People's Hospital, Beijing, 100044, China.
  • 4 Key Laboratory of Epigenetic Regulation and Intervention, Institute of Biophysics, Chinese Academy of Sciences, 15 Datun Road, Beijing, 100101, China.
  • 5 University of Chinese Academy of Sciences, 19 Yuquan Road, Beijing, 100049, China.
  • 6 Western Institute of Health Data Science, 28 High Tech Avenue, Chongqing, 401329, China.
  • 7 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.
PMID: 39716927 DOI: 10.1002/advs.202411740
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.

Keywords

N‐ glycosylation modification; cathepsin D; colorectal cancer; liver metastasis.

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