Jul 8, 2020

CXCL5 promotes gastric cancer metastasis by inducing epithelial-mesenchymal transition and activating neutrophils

Oncogenesis
Zheying MaoXu Zhang

Abstract

Deregulated expression of chemokines in tumor microenvironment contributes to tumor metastasis by targeting distinct cells. Epithelial-derived neutrophil-activating peptide-78 (ENA78/CXCL5) is upregulated in many cancers and involved in tumor progression. The role and underlying mechanism of CXCL5 in gastric cancer (GC) metastasis remain unclear. In this study, we reported that the expression of CXCL5 was elevated in tumor tissues and positively associated with lymphatic metastasis and tumor differentiation. Stimulation by recombinant human CXCL5 (rhCXCL5) induced epithelial-mesenchymal transition (EMT) in GC cells through the activation of ERK pathway, which enhanced their migration and invasion abilities. The culture supernatant from tumor tissues also enhanced the migration and invasion abilities of GC cells, however, this effect was reversed by pre-treatment with CXCL5 neutralizing antibody. Further studies showed that rhCXCL5 could induce the expression of IL-6 and IL-23 in neutrophils through the activation of ERK and p38 signaling pathways, which in turn facilitated GC cell migration and invasion. The culture supernatant from tumor tissues showed similar effects on neutrophils in a CXCL5-dependent manner. Blockade of IL-...Continue Reading

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Mentioned in this Paper

Mitogen-Activated Protein Kinases
In Vivo
Interleukin-6
Neoplasm Metastasis
Malignant Neoplasms
Antibodies, Neutralizing
Supernatant
Tumor Tissue Sample
Recombinant Proteins
Migration, Cell

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