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Roles of intercellular cell adhesion molecule-1 (ICAM-1) in colorectal cancer: expression, functions, prognosis, tumorigenesis, polymorphisms and therapeutic implications.

ABSTRACT: Colorectal cancer (CRC) is a major global health problem and one of the major causes of cancer-related death worldwide. It is very important to understand the pathogenesis of CRC for early diagnosis, prevention strategies and identification of new therapeutic targets. Intercellular adhesion molecule-1 (ICAM-1, CD54) displays an important role in the the pathogenesis of CRC. It is a cell surface glycoprotein of the immunoglobulin (Ig) superfamily and plays an essential role in cell-cell, cell-extracellular matrix interaction, cell signaling and immune process. It is also expressed by tumor cells and modulates their functions, including apoptosis, cell motility, invasion and angiogenesis. The interaction between ICAM-1 and its ligand may facilitate adhesion of tumor cells to the vascular endothelium and subsequently in the promotion of metastasis. ICAM-1 expression determines malignant potential of cancer. In this review, we will discuss the expression, function, prognosis, tumorigenesis, polymorphisms and therapeutic implications of ICAM-1 in CRC.

SUBMITTER: Qiu Z

PROVIDER: S-EPMC9728583 | biostudies-literature | 2022

REPOSITORIES: biostudies-literature

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Roles of intercellular cell adhesion molecule-1 (ICAM-1) in colorectal cancer: expression, functions, prognosis, tumorigenesis, polymorphisms and therapeutic implications.

Qiu Zhiyuan Z Wang Yan Y Zhang Zhao Z Qin Rong R Peng Yong Y Tang Weifeng W Xi Yan Y Tian Guangyu G Zhang Yeqing Y

Frontiers in oncology 20221123

Colorectal cancer (CRC) is a major global health problem and one of the major causes of cancer-related death worldwide. It is very important to understand the pathogenesis of CRC for early diagnosis, prevention strategies and identification of new therapeutic targets. Intercellular adhesion molecule-1 (ICAM-1, CD54) displays an important role in the the pathogenesis of CRC. It is a cell surface glycoprotein of the immunoglobulin (Ig) superfamily and plays an essential role in cell-cell, cell-ext ...[more]

PMID: 36505809

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Project description:Simple Summary Intercellular adhesion molecule 1 (ICAM-1) is a protein produced by cells in blood vessel walls, as well as many other cell types. It localizes to the surface of these cells to allow them to communicate with adjacent cells. The production of ICAM-1 is induced by inflammation, such as occurs during infection, when one of its main functions is to direct white blood cells to the site of the infection. However, in autoimmune diseases and certain types of infection, ICAM-1 can be involved in directing cells to damage healthy tissue. ICAM-1 can also promote or protect against cancer, depending on the type of cancer and the cell populations that are producing it. In this review article, the ICAM1 gene and ICAM-1 protein are introduced, and their regulation is summarized. The roles of ICAM-1 in the immune system and a spectrum of diseases, as well as therapeutics that target ICAM-1, are discussed. Abstract Intercellular adhesion molecule 1 (ICAM-1) is a transmembrane protein in the immunoglobulin superfamily expressed on the surface of multiple cell populations and upregulated by inflammatory stimuli. It mediates cellular adhesive interactions by binding to the β2 integrins macrophage antigen 1 and leukocyte function-associated antigen 1, as well as other ligands. It has important roles in the immune system, including in leukocyte adhesion to the endothelium and transendothelial migration, and at the immunological synapse formed between lymphocytes and antigen-presenting cells. ICAM-1 has also been implicated in the pathophysiology of diverse diseases from cardiovascular diseases to autoimmune disorders, certain infections, and cancer. In this review, we summarize the current understanding of the structure and regulation of the ICAM1 gene and the ICAM-1 protein. We discuss the roles of ICAM-1 in the normal immune system and a selection of diseases to highlight the breadth and often double-edged nature of its functions. Finally, we discuss current therapeutics and opportunities for advancements.

Project description:Ulcerative colitis (UC) is a chronic inflammatory bowel disease that primarily affects the mucosal layer of the colon (large intestine). However, the relationship between Intercellular Adhesion Molecule-1 (ICAM1), SELL and UC is unclear. The UC datasets, GSE87466 and GSE36807, were downloaded from the gene expression omnibus database. The R package limma was utilized to identify differentially expressed genes (DEGs). Weighted gene co-expression network analysis was conducted. The construction and analysis of protein-protein interaction network, functional enrichment analysis, gene set enrichment analysis, and comparative toxicogenomics database analysis were performed. TargetScan was employed to screen miRNAs regulating central DEGs. Western blot (WB) was used to verify. A total of 2118 DEGs were identified in our study. Gene ontology analysis indicated their enrichment primarily in immune system processes, cellular responses to chemical stimuli, responses to organic substances, responses to external stimuli, and immune responses. Kyoto Encyclopedia of Genes and Genomes analysis revealed that the target cells were mainly enriched in chemokine signaling pathways and TNF signaling pathways. Gene set enrichment analysis enrichment analysis showed significant enrichment in chemokine signaling pathways and cell adhesion molecules. In the Metascape enrichment project, gene ontology terms included regulation of cell activation and positive regulation of immune response. Through the construction and analysis of a protein-protein interaction network, we identified 11 core genes (ICAM1, SELL, CD44, CD40, CCR7, CXCL8, CD19, CCL4, CD274, IL7R, IL1B). We found that the core genes (ICAM1, SELL) were highly expressed in UC samples and lowly expressed in normal samples, suggesting their potential regulatory roles in UC. These core genes were associated with lymphoproliferative disorders, inflammation and necrosis. WB results confirmed the high expression of ICAM1 and SELL in UC. ICAM1 and SELL are highly expressed in UC, and the higher the ICAM1 and SELL genes, the worse the prognosis.

Dataset Information

Roles of intercellular cell adhesion molecule-1 (ICAM-1) in colorectal cancer: expression, functions, prognosis, tumorigenesis, polymorphisms and therapeutic implications.

Publications

Roles of intercellular cell adhesion molecule-1 (ICAM-1) in colorectal cancer: expression, functions, prognosis, tumorigenesis, polymorphisms and therapeutic implications.

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