CXCL1 promotes cell migration in hepatocellular carcinoma by regulating the miR-30b-5p/ICAM-1 axis.

Hepatocellular carcinoma (HCC) is a highly lethal cancer with a growing global incidence and is often associated with poor prognosis due to its tendency to metastasize. Intercellular adhesion molecule (ICAM) 1 is a transmembrane protein found in various cancer cells and is associated with the spread of cancer and poor prognosis. Chemokine (C-X-C motif) ligand 1 (CXCL1) is a chemokine that significantly affects the cell motility of various cancers. However, the role of CXCL1 in ICAM-1 expression and in metastasis of hepatocellular carcinoma remains unclear. We determined that CXCL1 expression is positively and significantly associated with advanced-stage tumors in the HCC tissue array. Kaplan-Meier analysis revealed worse overall survival rates in the high CXCL1 expression group, suggesting its potential as a biomarker for cancer progression and stimulating hepatocellular carcinoma cells with CXCL1 enhanced migration abilities by upregulating ICAM-1 expression. CXCL1 was shown to enhance ICAM-1-dependent cell motility by inhibiting miR-30b-5p. This study provides novel evidence that CXCL1 could serve as a therapeutic target for metastasis in hepatocellular carcinoma.

Acetylshikonin induces necroptosis via the RIPK1/RIPK3-dependent pathway in lung cancer.

Despite advances in therapeutic strategies, lung cancer remains the leading cause of cancer-related death worldwide. Acetylshikonin is a derivative of the traditional Chinese medicine Zicao and presents a variety of anticancer properties. However, the effects of acetylshikonin on lung cancer have not been fully understood yet. This study explored the mechanisms underlying acetylshikonin-induced cell death in non-small cell lung cancer (NSCLC). Treating NSCLC cells with acetylshikonin significantly reduced cell viability, as evidenced by chromatin condensation and the appearance of cell debris. Acetylshikonin has also been shown to increase cell membrane permeability and induce cell swelling, leading to an increase in the population of necrotic cells. When investigating the mechanisms underlying acetylshikonin-induced cell death, we discovered that acetylshikonin promoted oxidative stress, decreased mitochondrial membrane potential, and promoted G2/M phase arrest in lung cancer cells. The damage to NSCLC cells induced by acetylshikonin resembled results involving alterations in the cell membrane and mitochondrial morphology. Our analysis of oxidative stress revealed that acetylshikonin induced lipid oxidation and down-regulated the expression of glutathione peroxidase 4 (GPX4), which has been associated with necroptosis. We also determined that acetylshikonin induces the phosphorylation of receptor-interacting serine/threonine-protein kinase 1 (RIPK1)/RIPK3 and mixed lineage kinase domain-like kinase (MLKL). Treatment with RIPK1 inhibitors (necrostatin-1 or 7-Cl-O-Nec-1) significantly reversed acetylshikonin-induced MLKL phosphorylation and NSCLC cell death. These results indicate that acetylshikonin activated the RIPK1/RIPK3/MLKL cascade, leading to necroptosis in NSCLC cells. Our findings indicate that acetylshikonin reduces lung cancer cells by promoting G2/M phase arrest and necroptosis.

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

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 PLCß/PKCα/c-Src phosphorylation. Furthermore, CX3CL1 enhanced activator protein-1 (AP-1) activity. The CX3CR1 mAb and PLCß, 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 PLCß/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.