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<p>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 <InlineEquation ID="IEq3"> <InlineMediaObject> <ImageObject Color="BlackWhite" FileRef="40203_2025_417_Article_IEq1.gif" Format="GIF" Height="17" Rendition="HTML" Resolution="72" Type="Linedraw" Width="42" /> </InlineMediaObject> <EquationSource Format="TEX">\(\upalpha _{\textrm{M}}\upbeta _{2}\)</EquationSource> </InlineEquation> (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 <InlineEquation ID="IEq4"> <InlineMediaObject> <ImageObject Color="BlackWhite" FileRef="40203_2025_417_Article_IEq4.gif" Format="GIF" Height="10" Rendition="HTML" Resolution="72" Type="Linedraw" Width="13" /> </InlineMediaObject> <EquationSource Format="TEX">\(\upalpha \)</EquationSource> </InlineEquation>I domain of integrin <InlineEquation ID="IEq5"> <InlineMediaObject> <ImageObject Color="BlackWhite" FileRef="40203_2025_417_Article_IEq4.gif" Format="GIF" Height="10" Rendition="HTML" Resolution="72" Type="Linedraw" Width="13" /> </InlineMediaObject> <EquationSource Format="TEX">\(\upalpha \)</EquationSource> </InlineEquation>M subunit. They commonly consist of <InlineEquation ID="IEq6"> <InlineMediaObject> <ImageObject Color="BlackWhite" FileRef="40203_2025_417_Article_IEq6.gif" Format="GIF" Height="17" Rendition="HTML" Resolution="72" Type="Linedraw" Width="13" /> </InlineMediaObject> <EquationSource Format="TEX">\(\upbeta \)</EquationSource> </InlineEquation>-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 <InlineEquation ID="IEq7"> <InlineMediaObject> <ImageObject Color="BlackWhite" FileRef="40203_2025_417_Article_IEq1.gif" Format="GIF" Height="17" Rendition="HTML" Resolution="72" Type="Linedraw" Width="42" /> </InlineMediaObject> <EquationSource Format="TEX">\(\upalpha _{\textrm{M}}\upbeta _{2}\)</EquationSource> </InlineEquation> 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.</p>

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In silico framework about prediction of collagen-derived matrikine generation and its ligand function binding to integrin \(\upalpha _{\textrm{M}}\upbeta _{2}\) for malignancy of colon cancer

  • 期刊论文

  • 发表日期：

    2025年9月4日

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  • Yun Shin,
  • Jin-Ku Lee

摘要

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 \(\upalpha _{\textrm{M}}\upbeta _{2}\) (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 \(\upalpha \) I domain of integrin \(\upalpha \) M subunit. They commonly consist of \(\upbeta \) -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 \(\upalpha _{\textrm{M}}\upbeta _{2}\) 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.