Abstract
Colon cancer accounts for the second leading cause of cancer-associated death worldwide. Since the metastasis contributes to its malignancy, targeting the extracellular matrix (ECM) remodeling is critical for its therapy. Most research had focused on the native form of the structural ECM proteins, termed core matrisomes, to find out the relationship of the TME to colon cancer progression. This study computationally predicted the generation and function of their bioactive fragments, termed matrikines, as ligands to their cognate integrin receptors. Type I (COL1A1 and COL1A2) and III (COL3A1) as the precursor, Membrane type-1 matrix metalloproteinase (MMP14) as the cleavage enzyme, integrin [Formula: see text] (macrophage-1 antigen, Mac-1) as the receptor, and caldesmon (CALD1) as the downstream effector were designated as each candidate. After the computational cleavage of the collagen, 3D structure prediction of the generated fragments and the docking simulation with the integrin receptor expected two fragments, each from COL1A1 and COL3A1, to be the significant ligand for binding to [Formula: see text]I domain of integrin [Formula: see text]M subunit. They commonly consist of [Formula: see text]-sheet and loop as the major motifs, which also belong to the binding main of the previously established ligands, such as ICAM-1 and pleiotrophin. The structural similarity between the binding domains from each ligand might support our framework for the overall prediction. Given the integrin [Formula: see text] as the well-known cell-surface marker of the phagocytic cells, our study suggests targeting the proposed candidates for immunotherapy during the colon cancer metastasis. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s40203-025-00417-2.