IADR Abstract Archives
CXCL8 Promotes Oral Cancer Metastasis via MMP1 and JAK1/STAT3
Objectives: Oral cancer is a highly aggressive malignancy with frequent lymph node metastasis, leading to poor prognosis. This study investigates the molecular mechanism by which CXCL8 promotes oral cancer metastasis.
Methods: GEO database analysis was conducted to compare CXCL8 expression in normal oral tissues and oral cancer tissues. Cell migration and wound healing assays were used to evaluate the effect of CXCL8 on cell migration and invasion. The role of MMP1 was explored using qPCR and transfection of MMP1 shRNA. The involvement of CXCR1, CXCR2, and JAK1/STAT3 pathways was determined using specific inhibitors and antibody array analysis. The relationship between CXCL8 and miRNAs (hsa-miR-145-5p and hsa-miR-526b-5p) was examined via database analysis and qPCR.
Results: CXCL8 expression was significantly elevated in oral cancer tissues and correlated with poor patient survival. Recombinant CXCL8 enhanced cell migration and invasion, while highly invasive oral cancer cell lines exhibited higher CXCL8 expression. CXCL8 increased MMP1 expression, and knockdown of MMP1 reversed CXCL8-induced cell migration. These results highlight the connection between MMP1 and CXCL8 in promoting oral cancer metastasis. Pretreatment with CXCR1/2 inhibitors reduced CXCL8-induced cell migration and MMP1 expression. Antibody array analysis revealed that CXCL8 activated JAK1/STAT3 phosphorylation, and JAK1/STAT3 inhibitors attenuated CXCL8-induced cell migration and MMP1 expression. CXCL8 also reduced the expression of hsa-miR-145-5p and hsa-miR-526b-5p, which target MMP1.
Conclusions: CXCL8 promotes oral cancer metastasis by upregulating MMP1 expression via CXCR1/2 and JAK1/STAT3 pathways while modulating miRNAs. These findings suggest CXCL8 as a promising therapeutic target for oral cancer metastasis.
Methods: GEO database analysis was conducted to compare CXCL8 expression in normal oral tissues and oral cancer tissues. Cell migration and wound healing assays were used to evaluate the effect of CXCL8 on cell migration and invasion. The role of MMP1 was explored using qPCR and transfection of MMP1 shRNA. The involvement of CXCR1, CXCR2, and JAK1/STAT3 pathways was determined using specific inhibitors and antibody array analysis. The relationship between CXCL8 and miRNAs (hsa-miR-145-5p and hsa-miR-526b-5p) was examined via database analysis and qPCR.
Results: CXCL8 expression was significantly elevated in oral cancer tissues and correlated with poor patient survival. Recombinant CXCL8 enhanced cell migration and invasion, while highly invasive oral cancer cell lines exhibited higher CXCL8 expression. CXCL8 increased MMP1 expression, and knockdown of MMP1 reversed CXCL8-induced cell migration. These results highlight the connection between MMP1 and CXCL8 in promoting oral cancer metastasis. Pretreatment with CXCR1/2 inhibitors reduced CXCL8-induced cell migration and MMP1 expression. Antibody array analysis revealed that CXCL8 activated JAK1/STAT3 phosphorylation, and JAK1/STAT3 inhibitors attenuated CXCL8-induced cell migration and MMP1 expression. CXCL8 also reduced the expression of hsa-miR-145-5p and hsa-miR-526b-5p, which target MMP1.
Conclusions: CXCL8 promotes oral cancer metastasis by upregulating MMP1 expression via CXCR1/2 and JAK1/STAT3 pathways while modulating miRNAs. These findings suggest CXCL8 as a promising therapeutic target for oral cancer metastasis.