LDHA/Hedgehog signaling pathway axis regulates lung metastasis in osteosarcoma

Osteosarcoma has a strong tendency of lung metastasis and patients with metastases have poor prognoses. Lactate Dehydrogenase A subunit (LDHA) is one of the key enzymes in glycolysis and is known to be involved in progression and metastases of various cancers.

Here, we showed that Ldha knockdown suppressed cell migration and invasion in vitro in murine osteosarcoma cells and decreased lung metastases in vivo. Subsequent RNA-seq analysis revealed that Ldha knockdown was associated with downregulation of the Hedgehog signaling pathway and we demonstrated that pharmacological inhibition of the Hedgehog signaling pathway with vismodegib also suppressed cell migration, invasion and lung metastases in murine osteosarcoma cells as well as Ldha knockdown.