CX3CL1 induces cell migration and invasion through ICAM‐1 expression in oral squamous cell carcinoma cells

Abstract

Human oral squamous cell carcinoma (OSCC) has been associated with a relatively low survival rate over the years and is characterized by a poor prognosis. C‐X3‐C motif chemokine ligand 1 (CX3CL1) has been involved in advanced migratory cells. Overexpressed CX3CL1 promotes several cellular responses related to cancer metastasis, including cell movement, migration and invasion in tumour cells. However, CX3CL1 controls the migration ability, and its molecular mechanism in OSCC remains unknown. The present study confirmed that CX3CL1 increased cell movement, migration and invasion. The CX3CL1‐induced cell motility is upregulated through intercellular adhesion molecule‐1 (ICAM‐1) expression in OSCC cells. These effects were significantly suppressed when OSCC cells were pre‐treated with CX3CR1 monoclonal antibody (mAb) and small‐interfering RNA (siRNA). The CX3CL1‐CX3CR1 axis activates promoted PLCβ/PKCα/c‐Src phosphorylation. Furthermore, CX3CL1 enhanced activator protein‐1 (AP‐1) activity. The CX3CR1 mAb and PLCβ, PKCα, c‐Src inhibitors reduced CX3CL1‐induced c‐Jun phosphorylation, c‐Jun translocation into the nucleus and c‐Jun binding to the ICAM‐1 promoter. The present results reveal that CX3CL1 induces the migration of OSCC cells by promoting ICAM‐1 expression through the CX3CR1 and the PLCβ/PKCα/c‐Src signal pathway, suggesting that CX3CL1‐CX3CR1‐mediated signalling is correlated with tumour motility and appealed to be a precursor for prognosis in human OSCC.

Construction of a novel prognostic model in skin cutaneous melanoma based on chemokines-related gene signature

“…Among them, CX3CL1 is the most prevalent and has recently been discovered as a pro-angiogenic factor in myeloma patients 42 . It has been reported that CX3CL1 plays a crucial role in regulating cell adhesion, migration, and survival of human cancer cells 43 – 45 . ICAM-1 also plays a key role in cell adhesion to endothelium and tumor development, as well as cell proliferation, invasion, and angiogenesis.…”

CX3CL1 (Fractalkine)-CX3CR1 Axis in Inflammation-Induced Angiogenesis and Tumorigenesis

“…Imai et al (1997) identified a functional high-affinity CX3CL1 receptor, named V28, which was later renamed CX3CR1 [42]. Signaling through CX3CR1, which is the only known FKN receptor with documented function, is responsible for the adhesive and chemoattractant properties of CX3CL1 [42,43,[49][50][51].…”

“…The direct biological actions of both forms of fractalkine, adhesive for membrane-bound FKN and chemotactic for sFKN, are the result of interaction with the dedicated CX3C motif chemokine receptor 1 (CX3CR1, previously designated V28), also known as the fractalkine receptor or G-protein coupled receptor 13 (GPR13) [42,43,[49][50][51]. Noticeably, the existence of the sole receptor for CX3CL1 makes it much easier to interpret the observed biological effects related to this chemotactic cytokine with respect to the CX3CL1/CX3CR1 axis.…”