[en] Pancreatic cancer (PDAC) remains a deadly malignancy with no efficient therapy available up-to-date. Glycolysis is the main provider of energetic substrates to sustain cancer dissemination of PDAC. Accordingly, altering the glycolytic pathway is foreseen as a sound approach to trigger pancreatic cancer regression. Here, we show for the first time that high TGFBI expression in PDAC patients is associated with a poor outcome. We demonstrate that, although usually secreted by stromal cells, PDAC cells synthesize and secrete TGFBI in quantity correlated with their migratory capacity. Mechanistically, we show that TGFBI activates FAK signaling pathway through its binding to integrin αVβ5, leading to a significant enhancement of glycolysis and to the acquisition of an invasive phenotype. Finally, we show that TGFBI silencing significantly inhibits PDAC tumor development in a chick chorioallantoic membrane assay model. Our study highlights TGFBI as an oncogenic ECM interacting protein that bears the potential to serve as a target for new anti-PDAC therapeutic strategies.
Costanza, Brunella ; Université de Liège - ULiège > Département des sciences biomédicales et précliniques > GIGA-R : Labo de recherche sur les métastases
Rademaker, Gilles ; Université de Liège - ULiège > Département des sciences biomédicales et précliniques > Biologie générale et cellulaire
Tiamiou, Assia ; Université de Liège - ULiège > Département des sciences biomédicales et précliniques > Biologie générale et cellulaire
De Tullio, Pascal ; Université de Liège - ULiège > Département de pharmacie > Chimie pharmaceutique
Leenders, Justine ; Université de Liège - ULiège > Département des sciences cliniques > Labo de biologie des tumeurs et du développement
Bellier, Justine ; Université de Liège - ULiège > Cancer-Metastases Research Laboratory
Bianchi, Elettra ; Université de Liège - ULiège > Département des sciences biomédicales et précliniques > Département des sciences biomédicales et précliniques
Delvenne, Philippe ; Université de Liège - ULiège > Département des sciences biomédicales et précliniques > Anatomie et cytologie pathologiques
Bellahcene, Akeila ; Université de Liège - ULiège > Cancer-Metastases Research Laboratory
Peulen, Olivier ✱; Université de Liège - ULiège > Département des sciences biomédicales et précliniques > Département des sciences biomédicales et précliniques
Castronovo, Vincenzo ✱; Université de Liège - ULiège > Département des sciences biomédicales et précliniques > Biologie générale et cellulaire
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