Extent of N-glycosylation of the metalloproteinase inhibitor and cytokine TIMP-1 determines pancreatic cancer cell proliferation and survival via CD63.

ABSTRACT: Glycosylation emerges as a critical determinant of protein function in cancer, yet its impact on multifunctional secreted factors remains understudied. Here, we identified tissue inhibitor of metalloproteinases-1 (TIMP-1), a glycoprotein with glycosylation sites at N30 and N78 harboring both canonical antiproteolytic and noncanonical cytokine-like activity, as one of the most upregulated secreted glycoproteins circulating in the blood of pancreatic cancer (PC) patients. Whereas plasma from healthy donors contained similar amounts of double-glycosylated (TIMP-1^glyc1/1), single- glycosylated (N78 and not N30) (TIMP-1^glyc0/1), and nonglycosylated (TIMP-1^glyc0/0) TIMP-1, TIMP-1^glyc1/1 predominated in plasma from PC patients. scRNAseq and in vitro val

SUBMITTER: Haußler D 

PROVIDER: S-EPMC12167790 | biostudies-literature | 2025 May

REPOSITORIES: biostudies-literature