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Broad targeting of the cell adhesion machinery - cancer cell detachment triggered by the alpha1-oleate complex

Chaudhuri, Arunima LU orcid ; Haq, Farhan LU ; Ambite, Ines LU orcid ; Nazari, Atefeh LU ; Sabari, Samudra LU ; Tavecchio, Michele LU ; Pedro Nbm Carneiro, Antonio LU ; Stenström, Olof LU ; Ahmadi, Shahram LU and Tran, Hien LU , et al. (2026) In Molecular Therapy
Abstract

A new approach to targeting cell adhesion in oncology was recently suggested by observations made in patients with bladder cancer. Intravesical alpha1-oleate treatment triggered rapid tumor cell detachment into the urine and a parallel reduction in tumor number and size. This study identified alpha1-oleate as a potent inhibitor of multiple cell adhesion families in shed cells and tumor biopsies from treated patients, confirmed in cellular models. Alpha1-oleate targeted claudins and focal adhesion constituents, disrupted tight junctions, focal adhesions and adherens junctions, but gap junctions or desmosomes were not affected. The effects on cell adhesion were dose dependent, with stronger cell detachment and broader inhibition of... (More)

A new approach to targeting cell adhesion in oncology was recently suggested by observations made in patients with bladder cancer. Intravesical alpha1-oleate treatment triggered rapid tumor cell detachment into the urine and a parallel reduction in tumor number and size. This study identified alpha1-oleate as a potent inhibitor of multiple cell adhesion families in shed cells and tumor biopsies from treated patients, confirmed in cellular models. Alpha1-oleate targeted claudins and focal adhesion constituents, disrupted tight junctions, focal adhesions and adherens junctions, but gap junctions or desmosomes were not affected. The effects on cell adhesion were dose dependent, with stronger cell detachment and broader inhibition of adhesion-associated genes in patients treated with 8.5 mM of alpha1-oleate than the 1.7 mM dose. These acute and sustained effects identify cell detachment as a contributor to the anti-tumor effects observed clinically. AlphaFold predictions identified claudins and the FAT domain of FAK as potential alpha1-oleate targets but inhibitors of claudin and FAK phosphorylation showed less potent effects than alpha1-oleate on cell detachment. The broad effect of alpha1-oleate on the cell adhesion machinery is unprecedented and suggests that therapeutic targeting of the cell adhesion machinery by alpha1-oleate should be further explored.

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organization
publishing date
type
Contribution to journal
publication status
epub
subject
in
Molecular Therapy
publisher
Nature Publishing Group
external identifiers
  • pmid:42798181
ISSN
1525-0024
DOI
10.1016/j.ymthe.2026.09.029
language
English
LU publication?
yes
additional info
Copyright © 2026 The Author(s). Published by Elsevier Inc. All rights reserved.
id
d4c07295-cf40-4601-b690-25377b3f3da2
date added to LUP
2026-10-09 13:26:38
date last changed
2026-10-09 13:44:39
@article{d4c07295-cf40-4601-b690-25377b3f3da2,
  abstract     = {{<p>A new approach to targeting cell adhesion in oncology was recently suggested by observations made in patients with bladder cancer. Intravesical alpha1-oleate treatment triggered rapid tumor cell detachment into the urine and a parallel reduction in tumor number and size. This study identified alpha1-oleate as a potent inhibitor of multiple cell adhesion families in shed cells and tumor biopsies from treated patients, confirmed in cellular models. Alpha1-oleate targeted claudins and focal adhesion constituents, disrupted tight junctions, focal adhesions and adherens junctions, but gap junctions or desmosomes were not affected. The effects on cell adhesion were dose dependent, with stronger cell detachment and broader inhibition of adhesion-associated genes in patients treated with 8.5 mM of alpha1-oleate than the 1.7 mM dose. These acute and sustained effects identify cell detachment as a contributor to the anti-tumor effects observed clinically. AlphaFold predictions identified claudins and the FAT domain of FAK as potential alpha1-oleate targets but inhibitors of claudin and FAK phosphorylation showed less potent effects than alpha1-oleate on cell detachment. The broad effect of alpha1-oleate on the cell adhesion machinery is unprecedented and suggests that therapeutic targeting of the cell adhesion machinery by alpha1-oleate should be further explored.</p>}},
  author       = {{Chaudhuri, Arunima and Haq, Farhan and Ambite, Ines and Nazari, Atefeh and Sabari, Samudra and Tavecchio, Michele and Pedro Nbm Carneiro, Antonio and Stenström, Olof and Ahmadi, Shahram and Tran, Hien and Brisuda, Antonin and Hacek, Jaromir and Babjuk, Marek and Svanborg, Catharina}},
  issn         = {{1525-0024}},
  language     = {{eng}},
  month        = {{09}},
  publisher    = {{Nature Publishing Group}},
  series       = {{Molecular Therapy}},
  title        = {{Broad targeting of the cell adhesion machinery - cancer cell detachment triggered by the alpha1-oleate complex}},
  url          = {{http://dx.doi.org/10.1016/j.ymthe.2026.09.029}},
  doi          = {{10.1016/j.ymthe.2026.09.029}},
  year         = {{2026}},
}