Fiche publication
Date publication
janvier 2023
Journal
Molecular oncology
Auteurs
Membres identifiés du Cancéropôle Est :
Dr AVEROUS Gerlinde
,
Pr BORG Christophe
,
Pr GHIRINGHELLI François
,
Mme TRUNTZER Caroline
,
Dr PEIXOTO Paul
,
Mme BOUARD Adeline
,
Dr VIENOT Angélique
,
Dr ASGAROV Kamal
,
Dr LOYON Romain
,
Pr BIBEAU Frédéric
,
Dr MOLIMARD Chloé
Tous les auteurs :
Vienot A, Monnien F, Truntzer C, Mougey V, Bouard A, Pallandre JR, Molimard C, Loyon R, Asgarov K, Averous G, Ghiringhelli F, Bibeau F, Peixoto P, Borg C
Lien Pubmed
Résumé
Pancreatic ductal adenocarcinoma (PDAC) is marked by molecular heterogeneity and poor prognosis. Among the stemness-related transcription factors, Spalt-like Transcription Factor 4 (SALL4) is correlated with unfavorable outcomes; however, its roles in PDAC remain unclear. SALL4 expression defines a PDAC subpopulation characterized by a shortened patient survival. Although SALL4 expression was mostly evaluated in tumor cells, our findings identify this embryonic transcription factor as a new biomarker in PDAC-derived stroma. Gene expression analysis reveals that the SALL4 PDAC subset is enriched in cancer stem cell properties and stromal enrichment pathways; notably, an interaction with cancer-associated fibroblasts (CAF) activated by TGF-β. A particular oncogenic network was unraveled where Netrin-1 and TGF-β1 collaborate to induce SALL4 expression in CAF and drive their cancer-stemness-promoting functions. A 7-gene stromal signature related to SALL4 PDAC samples was highlighted and validated by immunochemistry for prognosis and clinical application. This SALL4-related stroma discriminated pancreatic preinvasive from invasive lesions and was enriched in short-term survivors. Our results show that SALL4 transcriptional activity controls a molecular network defined by a specific stromal signature that characterizes PDAC invasiveness and worse clinical outcomes.
Mots clés
SALL4, TGF-β, fibroblast, pancreatic cancer
Référence
Mol Oncol. 2023 01 1;:
