Icam1-KO Mouse

ICAM1, also known as Intercellular Adhesion Molecule 1 and CD54, is a cell-surface glycoprotein in the immunoglobulin supergene family. It functions as an adhesion receptor, regulating leukocyte recruitment to inflammation sites. The NF-κB signaling pathway regulates its expression. ICAM1 transduces outside-in-signaling via its cytoplasmic domain's association with the actin cytoskeleton after ligand binding to its extracellular domain, playing a crucial role in inflammation, injury resolution, and tumorigenesis [6].

In cancer research, ICAM1 has been shown to have significant roles. In triple-negative breast cancer (TNBC), depletion of ICAM1 abrogates lung and bone colonization of TNBC cells. It initiates CTC cluster formation and trans-endothelial migration in lung metastasis by mediating homotypic tumor cell-tumor cell cluster formation and heterotypic tumor-endothelial adhesion. It also promotes metastasis by activating cell cycle and stemness-related pathways [1,4]. In colorectal cancer, Fusobacterium nucleatum enhances CRC cell adhesion to endothelial cells, promotes extravasation and metastasis by inducing ICAM1 expression through the ALPK1/NF-κB axis [2]. In gastric cancer, knockout of ICAM1 in gastric cancer stem cells (GCSCs) using CRISPR/iCas9 leads to loss of their migration, invasion, and metastasis capacity [5]. In melanoma, blocking ICAM1 reduces tumor size and metastasis in older mice, as age-dependent loss of HAPLN1 indirectly upregulates endothelial ICAM1, eroding vascular integrity [7].

In conclusion, ICAM1 is a key regulator in multiple biological processes, especially in inflammation and cancer metastasis. Gene knockout models, such as in TNBC, colorectal, gastric, and melanoma cells, have revealed its essential role in promoting cancer cell metastasis. Targeting ICAM1 could potentially be a therapeutic strategy for various cancers, as well as for diseases like sickle cell disease where it contributes to vaso-occlusion and inflammation [3].

References:

1. Taftaf, Rokana, Liu, Xia, Singh, Salendra, Varadan, Vinay, Liu, Huiping. 2021. ICAM1 initiates CTC cluster formation and trans-endothelial migration in lung metastasis of breast cancer. In Nature communications, 12, 4867. doi:10.1038/s41467-021-25189-z. https://pubmed.ncbi.nlm.nih.gov/34381029/

2. Zhang, Ying, Zhang, Lu, Zheng, Sheng, Si, Jianmin, Zhuo, Wei. . Fusobacterium nucleatum promotes colorectal cancer cells adhesion to endothelial cells and facilitates extravasation and metastasis by inducing ALPK1/NF-κB/ICAM1 axis. In Gut microbes, 14, 2038852. doi:10.1080/19490976.2022.2038852. https://pubmed.ncbi.nlm.nih.gov/35220887/

3. Gupta, Parul, Kumar, Ravindra. 2024. Targeting ICAM1 to Ameliorate Vaso-Occlusion and Inflammation in Sickle Cell Disease. In European journal of haematology, 113, 730-737. doi:10.1111/ejh.14313. https://pubmed.ncbi.nlm.nih.gov/39354752/

4. Chen, Mingcang, Wu, Chunyu, Fu, Zhengwei, Liu, Sheng. 2022. ICAM1 promotes bone metastasis via integrin-mediated TGF-β/EMT signaling in triple-negative breast cancer. In Cancer science, 113, 3751-3765. doi:10.1111/cas.15532. https://pubmed.ncbi.nlm.nih.gov/35969372/

5. Tinajero-Rodríguez, José Manuel, Ramírez-Vidal, Lizbeth, Becerril-Rico, Jared, Contreras-Paredes, Adriana, Ortiz-Sánchez, Elizabeth. 2024. ICAM1 (CD54) Contributes to the Metastatic Capacity of Gastric Cancer Stem Cells. In International journal of molecular sciences, 25, . doi:10.3390/ijms25168865. https://pubmed.ncbi.nlm.nih.gov/39201551/

6. Bui, Triet M, Wiesolek, Hannah L, Sumagin, Ronen. 2020. ICAM-1: A master regulator of cellular responses in inflammation, injury resolution, and tumorigenesis. In Journal of leukocyte biology, 108, 787-799. doi:10.1002/JLB.2MR0220-549R. https://pubmed.ncbi.nlm.nih.gov/32182390/

7. Marino-Bravante, Gloria E, Carey, Alexis E, Hüser, Laura, Chhabra, Yash, Weeraratna, Ashani T. 2024. Age-dependent loss of HAPLN1 erodes vascular integrity via indirect upregulation of endothelial ICAM1 in melanoma. In Nature aging, 4, 350-363. doi:10.1038/s43587-024-00581-8. https://pubmed.ncbi.nlm.nih.gov/38472454/