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Cell_Reyes et al_2026.pdf (32.86 MB)

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2026-04-15

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Si us plau utilitzeu sempre aquest identificador per citar o enllaçar aquest document: https://hdl.handle.net/2445/229918

Oncogenic and tumor-suppressive forces converge on a progenitor niche at the benign-to-malignant transition

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https://doi.org/10.1016/j.cell.2026.03.032

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The benign-to-malignant transition is a defining step in cancer progression. To investigate when and how malignancy initiation occurs and tissue reorganization proceeds, we combine single-cell and spatial transcriptomic profiling in mouse models of pancreatic ductal adenocarcinoma (PDAC) that capture spontaneous p53 loss. Among Kras-mutant cells, we find that oncogenic and tumor-suppressive programs, including those controlled by p53, CDKN2A, and SMAD4, are co-activated in a discrete progenitor-like population, engaging senescence-like responses. Using a framework we developed for spatial analysis, we show that a niche centered on these cells undergoes stepwise remodeling during tumor progression, mirroring invasive PDAC. Transient KRAS inhibition depletes progenitor-like cells and dismantles their niche, delaying malignancy initiation. Conversely, p53 suppression enables progenitor cell expansion, epithelial-mesenchymal reprogramming, and immune-privileged niche formation. These findings position the progenitor-like state at the convergence of cancer-driving mutations, plasticity, and tissue remodeling, revealing a critical window for intercepting malignancy.

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Articles publicats en revistes (Institut de Recerca Biomèdica (IRB Barcelona))

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REYES, José, et al. Oncogenic and tumor-suppressive forces converge on a progenitor niche at the benign-to-malignant transition. CELL. 2026. ISSN Reyes, José; Del Priore, Isabella; Chaikovsky, Andrea C.; Pasnuri, Nikhita; Elhossiny, Ahmed M.; Park, Jin; Weiler, Philipp; Krause, Tobias; Moorman,  (2026). Oncogenic and tumor-suppressive forces converge on a progenitor niche at the benign-to-malignant transition. CELL, (), -. DOI: 10.1016/j.cell.2026.03.032. [consulted: 7 of June of 2026]. Available at: https://hdl.handle.net/2445/229918

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