Multifaceted collagen-DDR1 signaling in cancer

In addition to immune cells and fibroblasts, the tumor microenvironment (TME) comprises an extracellular matrix (ECM) which contains collagens (COLs) whose architecture and remodeling dictate cancer development and progression. COL receptors expressed by cancer cells sense signals generated by microenvironmental alterations in COL state to regulate cell behavior and metabolism. Discoidin domain receptor 1 (DDR1) is a key sensor of COL fiber state and composition that controls tumor cell metabolism and growth, response to therapy, and patient survival. This review focuses on DDR1 to NRF2 signaling, its modulation of autophagy and macropinocytosis (MP), and its role in cancer and other diseases. Elucidating the regulation of DDR1 activity and expression under different pathophysiological conditions will facilitate the discovery of new therapeutics.