Collagenolysis-dependent DDR1 signalling dictates pancreatic cancer outcome

Menée in vitro et à l'aide de modèles murins d'adénocarcinome canalaire du pancréas, cette étude met en évidence un mécanisme par lequel le collagène de type 1, intact ou clivé par les métalloprotéases de la matrice extracellulaire, freine ou favorise la croissance tumorale et le processus métastatique via la voie mitochondriale

Résumé en anglais

Pancreatic ductal adenocarcinoma (PDAC) is a highly desmoplastic, aggressive cancer that frequently progresses and spreads by metastasis to the liver1. Cancer-associated fibroblasts, the extracellular matrix and type I collagen (Col I) support2,3 or restrain the progression of PDAC and may impede blood supply and nutrient availability4. The dichotomous role of the stroma in PDAC, and the mechanisms through which it influences patient survival and enables desmoplastic cancers to escape nutrient limitation, remain poorly understood. Here we show that matrix-metalloprotease-cleaved Col I (cCol I) and intact Col I (iCol I) exert opposing effects on PDAC bioenergetics, macropinocytosis, tumour growth and metastasis. Whereas cCol I activates discoidin domain receptor 1 (DDR1)–NF-