{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\nA wealth of studies has demonstrated that the collagen‐binding receptor tyrosine kinase DDR1 plays multifaceted roles in a broad range of physiological and pathological processes. Activation of DDR1 via its extracellular domain drives collagen fiber alignment that can enforce immune exclusion in tumors—impeding T‐cell penetration and promoting tumor growth—and orchestrates cell–matrix interactions across diverse cell types. In vascular smooth muscle, renal mesangial cells, and podocytes, DDR1 signaling regulates adhesion, migration, and matrix metalloproteinase production to control extracellular matrix turnover and tissue remodeling."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "1", "end_ref": "9"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nDDR1 activation further initiates intracellular signaling cascades—including Ras, PI3K/Akt, ERK, and NF‐κB pathways—that balance cell proliferation and differentiation, modulate cytoskeletal organization, and stabilize cell–cell adhesion. Through these mechanisms, DDR1 influences epithelial plasticity by stabilizing key junction proteins and contributes to the maturation of basement membranes essential for maintaining renal and mammary gland homeostasis."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "10", "end_ref": "21"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nDDR1 also acts as a critical mediator of tumor–stroma cross‐talk and tissue remodeling in cancers. In pancreatic and breast cancer models, collagen‐induced DDR1 signaling promotes the secretion of cytokines and chemokines that drive the recruitment of immune cells—such as neutrophils—and facilitates extracellular matrix deposition, fibrosis, and metastatic progression. 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