Carbonic anhydrase IX (CAIX) is a
hypoxia-induced
protein that is highly expressed in numerous human
cancers. However, the molecular mechanisms involved in CAIX and human
cervical cancer metastasis remain poorly understood. In this study, CAIX overexpression in SiHa cells increased cell migration and epithelial-to-mesenchymal transition (EMT). Silencing CAIX in the Caski cell line decreased the motility of cells and EMT. Furthermore, the
RNA-sequencing analysis identified a target gene, bifunctional 6-phosphofructo-2-
kinase/
fructose-2,6-bisphosphatase (PFKFB4), which is influenced by CAIX overexpression and knockdown. A positive correlation was found between CAIX expression and PFKFB4 levels in the
cervical cancer of the TCGA database. Mechanistically, CAIX overexpression activated the phosphorylation of
extracellular signal-regulated kinases (ERKs) to induce EMT and promote cell migration. In clinical results, human
cervical cancer patients with CAIXhigh/PFKFB4high expression in the late stage had higher rates of
lymph node metastasis and the shortest survival time. Our study found that CAIX overexpression increases PFKFB4 expression and EMT, promoting
cervical cancer cell migration. CAIX could contribute to
cervical cancer cell
metastasis and its inhibition could be a
cervical cancer treatment strategy.