Pubblicazioni

Autori:

Veghini, Lisa; Pasini, Davide; Fang, Rui; Delfino, Pietro; Filippini, Dea; Neander, Christian; Vicentini, Caterina; Fiorini, Elena; Lupo, Francesca; D'Agosto, Sabrina L; Carbone, Carmine; Agostini, Antonio; Piro, Geny; Rosa, Diego; Bevere, Michele; Markus, Peter; Behrens, Diana; Luchini, Claudio; Lawlor, Rita T; Scarpa, Aldo; Biffi, Giulia; Cheung, Phyllis F; Siveke, Jens T; Corbo, Vincenzo

Titolo:

Differential activity of MAPK signalling defines fibroblast subtypes in pancreatic cancer

Anno:

2024

Tipologia prodotto:

Articolo in Rivista

Tipologia ANVUR:

Articolo su rivista

Lingua:

Inglese

Formato:

Elettronico

Referee:

No

Nome rivista:

NATURE COMMUNICATIONS

ISSN Rivista:

2041-1723

N° Volume:

15

Numero o Fascicolo:

1

Intervallo pagine:

1-20

Parole chiave:

HEDGEHOG PATHWAY INHIBITOR, DUCTAL ADENOCARCINOMA, THERAPY, TUMOR, MYOFIBROBLASTS, MAINTENANCE, SUPPRESSION, DRIVES, GROWTH, KRAS

Breve descrizione dei contenuti:

: Fibroblast heterogeneity is increasingly recognised across cancer conditions. Given their important contribution to disease progression, mapping fibroblasts' heterogeneity is critical to devise effective anti-cancer therapies. Cancer-associated fibroblasts (CAFs) represent the most abundant cell population in pancreatic ductal adenocarcinoma (PDAC). Whether CAF phenotypes are differently specified by PDAC cell lineages remains to be elucidated. Here, we reveal an important role for the MAPK signalling pathway in defining PDAC CAF phenotypes. We show that epithelial MAPK activity promotes the myofibroblastic differentiation of CAFs by sustaining the expression and secretion of TGF-β1. We integrate single-cell profiling of post-perturbation transcriptional responses from mouse models with cellular and spatial profiles of human tissues to define a MAPKhigh CAF (mapCAF) phenotype. We show that this phenotype associates with basal-like tumour cells and reduced frequency of CD8+ T cells. In addition to elevated MAPK activity, this mapCAF phenotype is characterized by TGF-β signalling, hypoxia responsive signatures, and immunoregulatory gene programs. Furthermore, the mapCAF signature is enriched in myofibroblastic CAFs from various cancer conditions and correlates with reduced response to immune checkpoint inhibition in melanoma. Altogether, our data expand our knowledge on CAF phenotype heterogeneity and reveal a potential strategy for targeting myofibroblastic CAFs in vivo.

Note:

These authors contributed equally: Lisa Veghini, Davide Pasini, Rui Fang Supplementary information The online version contains supplementary material available at https://doi.org/10.1038/s41467-024-54975-8

Id prodotto:

142950

Handle IRIS:

11562/1146389

ultima modifica:

22 dicembre 2024

Citazione bibliografica:

Veghini, Lisa; Pasini, Davide; Fang, Rui; Delfino, Pietro; Filippini, Dea; Neander, Christian; Vicentini, Caterina; Fiorini, Elena; Lupo, Francesca; D'Agosto, Sabrina L; Carbone, Carmine; Agostini, Antonio; Piro, Geny; Rosa, Diego; Bevere, Michele; Markus, Peter; Behrens, Diana; Luchini, Claudio; Lawlor, Rita T; Scarpa, Aldo; Biffi, Giulia; Cheung, Phyllis F; Siveke, Jens T; Corbo, Vincenzo, Differential activity of MAPK signalling defines fibroblast subtypes in pancreatic cancer «NATURE COMMUNICATIONS» , vol. 15 , n. 1 , 2024 , pp. 1-20

Consulta la scheda completa presente nel repository istituzionale della Ricerca di Ateneo