Interleukin-8 promotes integrin β3 upregulation and cell invasion through PI3K/Akt pathway in hepatocellular carcinoma

Abstract

BackgroundInterleukin-8 (IL-8) plays a vital role in the invasion and metastasis of hepatocellular carcinoma (HCC), and is closely associated with poor prognosis of HCC patients. Integrin αvβ3, a member of the integrin family, has been reported to be overexpressed in cancer tissues and mediate the invasion and metastasis of HCC cells. However, the relationship between IL-8 and integrin αvβ3 in HCC and the underlying mechanism of IL-8 and integrin αvβ3 in the invasion of HCC remains unclear.MethodsThe expression of IL-8, integrin αv and integrin β3 in HCC cells and tissues was detected by quantitative real-time PCR, Western blot and immunohistochemistry. Transwell assay and Western blot was used to detect the invasiveness, the expression of integrin β3 and the activation of PI3K/Akt pathway of HCC cells pretreated with IL-8 knockdown or exogenous IL-8.ResultsIL-8, integrin αv and integrin β3 were overexpressed in highly metastatic HCC cell lines compared with low metastatic cell lines. There was a positive correlation between integrin β3 and IL-8 expression in HCC tissues. IL-8 siRNA transfection reduced HCC cell invasion and the levels of integrin β3, p-PI3K and p-Akt. IL-8 induced HCC cell invasion and integrin β3 expression was significantly inhibited by transfection with CXCR1 siRNA or CXCR2 siRNA. When we stimulated HCC cells with exogenous IL-8, cell invasion and the levels of integrin β3, p-PI3K, and p-Akt increased, which could be effectively reversed by adding PI3K inhibitor LY294002.ConclusionsOur results suggest that IL-8 promotes integrin β3 upregulation and the invasion of HCC cells through activation of the PI3K/Akt pathway. The IL-8/CXCR1/CXCR2/PI3K/Akt/integrin β3 axis may serve as a potential treatment target for patients with HCC.

Circ_0000215 Increases the Expression of CXCR2 and Promoted the Progression of Glioma Cells by Sponging miR-495-3p

“… 45 , 46 Interestingly, CXCR2 also affects tumor development by mediating PI3K/AKT signaling. 47 Here, our data revealed that miR-495-3p inhibited phosphorylated level of PI3K/Akt, while overexpressing circ_0000215 promoted the PI3K/Akt activation, which was consistent with CXCR2 expression, suggesting that circ_0000215/miR-495-3p could promote glioma progression via activating PI3K/Akt through CXCR2.…”

Comprehensive gene and pathway analysis of cervical cancer progression

“…The RIG-I-like receptor and Toll-like receptor signaling pathways were identified in phase II, and are associated with pattern-recognition receptors (91). In addition, several pathways, including 'focal adhesion', 'Rap1 signaling pathway', 'Ras signaling pathway', 'PI3K-Akt signaling pathway' and 'Proteoglycans in cancer' were associated with invasion and metastasis (92)(93)(94)(95)(96). The two common cancer-associated signaling pathways 'Pathways in cancer' and 'Proteoglycans in cancer', were enriched in phase III, while 70 pathways were significant enriched at phase IV (P<0.05).…”

Association between Inflammation and Function of Cell Adhesion Molecules Influence on Gastrointestinal Cancer Development

“…Chemokine (C-X-C motif) ligand 1 (CXCL1) secreted by tumor-associated lym-phatic endothelial cells induces integrin β1 to activate FAK/Akt signaling and promotes adhesion and metastasis of gastric cancer via MMP2/9 upregulation [121]. In HCC, IL-8 promotes invasive ability via the integrin β3-mediated PI3K/Akt pathway [122]. Gastrointestinal cancer is an inflammation-related disease.…”

“…Taken together, the data support the critical roles of cancer cell adhesion molecules in tumor growth, metastasis, and chemoresistance ( Table 2). L-selectin Metastasis [113] Liver cancer E-selectin Tumor growth, Angiogenesis [111] Integrins Gastric cancer integrin β4 SOX2/HIF-1α signaling, EGFR EMT, Glucose metabolism, gefitinib chemoresistance [117,118] integrin β1 CXCL1, FAK/Akt signaling, MMP2/9 Adhesion, Metastasis [121] Pancreatic cancer integrin α3β1 ZIP4, ZEB1, STAT3 signaling, JNK signaling pathway Chemoresistance [119] Integrin family galectin-3, IL-8, NF-κB signaling Promote tumor growth, Metastasis [125] Colorectal cancer integrin α2β1 CDH17, FAK and Ras pathways Proliferation, Metastasis [120] integrin β1 TLR4, PI3K/Akt pathway Adhesion, Metastasis [123] Liver cancer integrin β3 IL-8, PI3K/Akt pathway Invasion [122] integrin αvβ3 galectin-1, FAK/PI3K/Akt signaling EMT, Sorafenib resistance [124] 3.4. Programmed Death-Ligand 1…”