ICAM-1 promotes cancer progression by regulating SRC activity as an adapter protein in colorectal cancer

Abstract

Colorectal cancer (CRC) has a 5-year survival rate of <10%, as it can metastasize to the lungs and liver. Anticancer drugs and targeted therapies used to treat metastatic colorectal cancer have insufficient therapeutic efficacy and are associated with complications. Therefore, research to develop new targeted therapeutics is necessary. Here, we present a novel discovery that intracellular adhesion molecule-1 (ICAM-1) is a potential therapeutic target to enhance therapeutic effectiveness for CRC. ICAM-1 is an important regulator of cell–cell interactions and recent studies have shown that it promotes malignancy in several carcinomas. However, little is known about its effect on CRC. Therefore, we conducted a study to define the mechanism by which ICAM-1 acts. ICAM-1 is phosphorylated by tyrosine-protein kinase Met (c-MET), and phosphorylated ICAM-1 can interact with SRC to increase SRC activity. Consequently, ICAM-1 may further accelerate SRC signaling, promoting the malignant potential of cancer. In addition, treatment with antibodies targeting ICAM-1 showed excellent therapeutic effects in reducing metastasis and angiogenesis. These findings suggest for the first time that ICAM-1 is an important adapter protein capable of mediating the c-MET-SRC signaling axis. Therefore, ICAM-1 can be used as a novel therapeutic target and a metastatic marker for CRC.

TREM2 promotes glioma progression and angiogenesis mediated by microglia/brain macrophages

“…Some immune signaling genes which can modulate angiogenesis were also identified in the downregulated group (KEGG pathway category: signaling molecules and interaction; Figure 5c), including two cell adhesion molecules Icam1 (Lim et al, 2022) and Itgal (Silva et al, 2008; Zhang, Wang et al, 2022), chemokines Ccl12 and Ccl5 (Suffee et al, 2011; Wang et al, 2015), the chemokine receptor Ccr5 and inflammatory signaling adaptor Myd88 (Zhang et al, 2020). Based on the adjusted p value ( q value), these genes are downregulated in GBM from TREM2 KO animals (Figure 5e–i and Figure S3c,d).…”

“…The reduction of MHC gene cluster may suggest a reduced antigen presentation in GBM from KO animals compared to WT and may contribute to immune escape and impaired functions of CD4 + /CD8 + cells and NK cells in GBM (Burster et al, 2021;Kilian et al, 2023). Some immune signaling genes which can modulate angiogenesis were also identified in the downregulated group (KEGG pathway category: signaling molecules and interaction; Figure 5c), including two cell adhesion molecules Icam1 (Lim et al, 2022) and Itgal (Silva et al, 2008;, chemokines Ccl12 and Ccl5 (Suffee et al, 2011;Wang et al, 2015), the chemokine receptor Ccr5 and inflammatory signaling adaptor Myd88 (Zhang et al, 2020).…”

Proteomes of Residual Tumors in Curcumin-Treated Rats Reveal Changes in Microenvironment/Malignant Cell Crosstalk in a Highly Invasive Model of Mesothelioma

“…The implication of LRP1 (also known as CD91, encoded by Lrp1 ) in tumor immunosurveillance has been well documented, providing a highly efficient conduit for the cross-presentation of tumor antigens to T cells [ 72 ]. Among the proteins exhibiting a decrease, ICAM-1 (encoded by Icam1 ) represents an adhesive molecule also known to weaken the immune response in cancer cells in addition to its promoting action on cancer progression [ 73 ]. The protein tyrosine phosphatase CD45 (encoded by Ptprc ) was shown to affect the function of T and other immune cells, with a negative impact on the prognosis of lung adenocarcinoma [ 74 ].…”

DEAD-Box RNA Helicases DDX3X and DDX5 as Oncogenes or Oncosuppressors: A Network Perspective

“…ICAM-1 (intracellular adhesion molecule-1), when phosphorylated by the protein kinase c-MET, can interact with the Src kinase to increase its activity, promoting colorectal cancer progression [ 131 , 132 ]. It could be interesting to understand whether DDX3X affects ICAM-1 phosphorylation.…”