| Title: |
WNT7B drives a program for pancreatic cancer subtype switching and progression |
| Authors: |
Sprangers, Joep; Bugter, Jeroen M.; Xanthakis, Despina; Boekhout, Michiel; Kok, Rutger N.U.; Geurts,Veerle E.; Clevers, Hans; Brosens, Lodewijk A.A.; Dijk,Frederike; Rodríguez Colman, Maria J.; van der Vaart, Jelte Y.; Maurice, Madelon M.; CMM; Cancer; CMM Groep Maurice; CMM Groep Rodriguez Colman; Hubrecht Institute with UMC; Pathologie Pathologen staf; Regenerative Medicine and Stem Cells |
| Publication Year: |
2026 |
| Subject Terms: |
cancer; cell biology; functional aspects of cell biology; General |
| Description: |
Hyperactivation of WNT signaling is a hallmark of cancer, often driven by increased expression of WNT ligands. In pancreatic ductal adenocarcinoma (PDAC), elevated WNT7B and WNT10A correlate with aggressive, basal-like disease and poor patient survival, but the mechanisms underlying this association remain unclear. Using patient-derived organoids, we show that WNT7B promotes proliferation and maintains basal-like transcriptional states by preventing differentiation toward a more classical PDAC signature. Clonal WNT7B reporter organoids reveal that WNT-high cells are heterogeneously distributed and stably coexist with WNT-low/negative lineages. Hybrid co-cultures demonstrate that WNT7B-expressing cells support the survival and growth of neighboring WNT-negative cells via short-range, contact-dependent signaling. These findings highlight the functional importance of heterogeneous WNT7B/10A expression in driving PDAC aggressiveness and suggest that targeted WNT inhibition may shift tumors toward a more differentiated, less aggressive state, offering potential therapeutic benefit. |
| Document Type: |
article in journal/newspaper |
| File Description: |
application/pdf |
| Language: |
English |
| ISSN: |
2589-0042 |
| Relation: |
https://dspace.library.uu.nl/handle/1874/469553 |
| Availability: |
https://dspace.library.uu.nl/handle/1874/469553 |
| Rights: |
info:eu-repo/semantics/OpenAccess |
| Accession Number: |
edsbas.29B4B15C |
| Database: |
BASE |