Carbonic Anhydrase <scp>IX</scp> Induces Human Osteosarcoma Cell Metastasis by Activating <scp>HSPA6</scp> Expression Through the <scp>AMPK</scp> Signalling Pathway

Osteosarcoma(OS), the most common primary bone cancer, has high metastatic potential and a high mortality rate. Carbonic anhydrase IX (CAIX), a hypoxia-induced transmembrane protein, is highly expressed in numerous cancers. Over the past decades, scientists have made extensive efforts to determine the role of CAIX in various cancers. However, the effects of CAIX on the metastasis of OS cell lines remain unclear. We examined the effectiveness of CAIX for inducing the invasion and migration of human OS cells and the underlying molecular mechanisms. We established CAIX-overexpressing human OS cells and found markedly increased migratory and invasive abilities in HOS and U2OS cell lines. In addition, CAIX overexpression increased the messenger ribonucleic acid (mRNA) and protein expression levels of heat shock protein family A member 6 (HSPA6) and the phosphorylation of adenosine-monophosphate-activated protein kinase (AMPK) signalling proteins. With HSPA6 knockdown, U2OS cells exhibited significantly reduced migratory and invasive abilities. Moreover, treatment with an AMPK inhibitor (dorsomorphin) suppressed CAIX-induced HSPA6 expression and the metastasis of U2OS cells. In conclusion, the results indicate that CAIX overexpression mediates HSPA6 expression through the AMPK signalling pathway, which consequently induces the metastasis of OS cells.