Cell clusters are programmed towards a reductive metabolic state by adherence junctions Article Swipe
Uttkarsh Ayyangar
,
Janhavi Sathe
,
Md. Faiz Ahmad
,
Sunil Laxman
·
YOU?
·
· 2025
· Open Access
·
· DOI: https://doi.org/10.1101/2025.10.02.680172
YOU?
·
· 2025
· Open Access
·
· DOI: https://doi.org/10.1101/2025.10.02.680172
Solitary cells form stable clusters via cell-cell adhesion using adherens junctions. The role of these junctions in early cell-state changes as cells form clusters is unclear. Here, we uncover that the formation of cadherin junctions as cells cluster drives a ubiquitous metabolic reprogramming. This reprogramming enhances the pentose phosphate pathway (PPP) and NADPH production to augment a reductive state. Consequently, cell clusters stabilized by cadherin junctions have reduced intracellular reactive oxygen species (ROS), are resistant to exogenous ROS-inducing agents, and have reduced apoptotic markers. Mechanistically, this metabolic reprogramming is driven by the cadherin-dependent activation of NRF2. Blocking the cadherin junction-dependent metabolic program reverses clustered cells to resemble the solitary cell state, increasing cell death and enhancing sensitivity to exogenous ROS. These insights suggest a biochemical basis for adherens junctions mediating a reductive metabolic program as solitary cells form clusters, with implications for understanding multicellular organization and collective cell behavior.
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- article
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- en
- Landing Page
- https://doi.org/10.1101/2025.10.02.680172
- https://www.biorxiv.org/content/biorxiv/early/2025/10/03/2025.10.02.680172.full.pdf
- OA Status
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- References
- 53
- OpenAlex ID
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Cell clusters are programmed towards a reductive metabolic state by adherence junctionsWork title
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enPrimary language
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2025Year of publication
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2025-10-03Full publication date if available
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Uttkarsh Ayyangar, Janhavi Sathe, Md. Faiz Ahmad, Sunil LaxmanList of authors in order
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https://doi.org/10.1101/2025.10.02.680172Publisher landing page
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https://www.biorxiv.org/content/biorxiv/early/2025/10/03/2025.10.02.680172.full.pdfDirect link to full text PDF
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YesWhether a free full text is available
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greenOpen access status per OpenAlex
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https://www.biorxiv.org/content/biorxiv/early/2025/10/03/2025.10.02.680172.full.pdfDirect OA link when available
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