Collagenolysis-dependent DDR1 signalling dictates pancreatic cancer outcome.

ABSTRACT: 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) support^2,3 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 rece

SUBMITTER: Su H 

PROVIDER: S-EPMC9588640 | biostudies-literature | 2022 Oct

REPOSITORIES: biostudies-literature