C‐X‐C Motif Ligand 1 Induces Cell Migration by Upregulating ICAM‐1 Expression by Activating PI3K/Akt and NF‐κB Signaling Pathway in Liver Cancer

Abstract Human hepatocellular carcinoma (HCC) is the most common liver cancer and the third leading cause of cancer‐related deaths worldwide. HCC is a malignant tumor that can lead to intrahepatic and extrahepatic metastases. Intercellular adhesion molecule 1 (ICAM‐1) is involved in cancer metastasis. ICAM‐1 enhances cell‐cell interactions by promoting adhesion and facilitating cell movement within the extracellular matrix. Moreover, ICAM‐1 is more abundant in cancerous hepatocytes than in non‐cancerous ones. Chemokine (C‐X‐C motif) ligand 1 (CXCL1) is found in diverse cancers, including melanoma, breast, lung, pancreatic, colorectal, and prostate. Several studies show a correlation between CXCL1 overexpression and poor prognosis in cancer. CXCL1 has been identified as a candidate gene that could function as a clinically relevant biomarker in HCC. However, the role of CXCL1 in cancer metastasis in HCC is poorly delineated. In this study, Gene Expression Omnibus (GEO) database analysis revealed a positive correlation between CXCL1 level and the progression and metastasis of hepatocellular carcinoma patients. CXCL1 treatment facilitates cell movement through inducing ICAM‐1 expression. The Phosphoinositide 3‐kinase (PI3K)/Akt/Nuclear Factor kappa B (NF‐kB) signaling pathway plays a crucial role in CXCL1‐regulated ICAM‐1 production and cell motility. Thus, CXCL1 represents a promising therapeutic target for treating metastatic hepatocellular carcinoma.