Evidence map›Paper›PMID 41581870›Full record

ArticleThe Journal of biological chemistry2026

The protease cathepsin K can debulk the cancer glycocalyx.

Angel Kuo, Gabrielle S Tender, William D Chow, Nicholas M Riley, Ke Chloe Wen, Sangwoo Park, Justin H Paek, David S Roberts, Egan L Peltan, Matthew J Paszek and 1 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in The Journal of biological chemistry, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 papers.

0numbers the graph read from it
0cells of the map it votes in
2citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

2 citing papers in PubMed.

  1. Discovery of a secretedGut microbes · 2026
    Article
  2. Review
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

11 authors.

Angel KuoDepartment of Chemistry and Sarafan ChEM-H, Stanford University, Stanford, California, USA.
Gabrielle S TenderDepartment of Chemistry and Sarafan ChEM-H, Stanford University, Stanford, California, USA.
William D ChowDepartment of Chemistry and Sarafan ChEM-H, Stanford University, Stanford, California, USA.
Nicholas M RileyDepartment of Chemistry and Sarafan ChEM-H, Stanford University, Stanford, California, USA.
Ke Chloe WenDepartment of Chemistry and Sarafan ChEM-H, Stanford University, Stanford, California, USA.
Sangwoo ParkField of Biophysics, Cornell University, Ithaca, New York, USA; Robert Frederick Smith School of Chemical and Biomolecular Engineering, Cornell University, Ithaca, New York, USA.
Justin H PaekNancy E. and Peter C. Meinig School of Biomedical Engineering, Cornell University, Ithaca, New York, USA.
David S RobertsDepartment of Chemistry and Sarafan ChEM-H, Stanford University, Stanford, California, USA.
Egan L PeltanDepartment of Chemistry and Sarafan ChEM-H, Stanford University, Stanford, California, USA.
Matthew J PaszekField of Biophysics, Cornell University, Ithaca, New York, USA; Robert Frederick Smith School of Chemical and Biomolecular Engineering, Cornell University, Ithaca, New York, USA; Nancy E. and Peter C. Meinig School of Biomedical Engineering, Cornell University, Ithaca, New York, USA.
Carolyn R BertozziDepartment of Chemistry and Sarafan ChEM-H, Stanford University, Stanford, California, USA; Howard Hughes Medical Institute, Stanford, California, USA. Electronic address: bertozzi@stanford.edu.

Funding

Physical Resistance to Immune Cell Attack by the Cellular GlycocalyxR01CA276398 · NCI · CORNELL UNIVERSITY · PI Matthew J Paszek · 2023 to 2026
$1.8M
The integrated mechanobiology and glycobiology of bone metastasisR01CA297166 · NCI · CORNELL UNIVERSITY · PI Claudia Fischbach, Matthew J Paszek · 2025 to 2026
$1.2M
Capturing the Holistic Glycocode through Systems GlycobiologyR00GM147304 · NIGMS · UNIVERSITY OF WASHINGTON · PI Nicholas M Riley · 2024 to 2026
$747k
NCI NIH HHS R01 CA276398NCI NIH HHS R01 CA297166NIGMS NIH HHS R00 GM147304
6 · The paper itself

Abstract

The cancer glycocalyx is characterized by the overexpression of large glycoconjugates, including mucins, proteoglycans, and polysialic acid, which collectively increase glycocalyx thickness and stiffness to promote tumor survival, metastasis, and progression. Previous work demonstrated that enzymatic degradation of cancer cell-surface mucins reduced tumor burden and metastasis in mouse models of breast cancer, thus validating glycocalyx remodeling as a therapeutic strategy. However, this work relied on an engineered bacterial mucin-selective protease, or mucinase, which does not degrade other bulky glycoconjugates and raises immunogenicity concerns because of its bacterial origin. A human enzyme that can degrade cell-surface mucins and other bulky glycoconjugates would address both limitations. We screened all 15 human cathepsins for their ability to degrade purified and cell-surface mucins, since multiple cathepsins have previously been shown to degrade mucins within regions of dense glycosylation. We found that cathepsin K (CTSK) uniquely degrades cell-surface mucins, proteoglycans, and polysialylated glycoproteins, and we demonstrated that CTSK reduces total glycocalyx thickness. These findings establish CTSK as a promising starting point for the development of a glycocalyx-debulking enzyme for cancer therapeutics.

Indexed as

Cathepsin KGlycocalyxNeoplasmsAnimalsHumansMucinsCathepsin KMucinscancer therapycathepsinglycobiologyglycocalyxglycoproteinglycosaminoglycanmucinmucinaseproteaseproteoglycan

Identifiers

PMID41581870
PMCPMC12969431

What OpenQuestion holds

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Registered trials

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.