Inhibition of Aurora kinases induces apoptosis and autophagy via AURKB/p70S6K/RPL15 axis in human leukemia cells

Leukemia is a common malignancy of blood cells with poor prognosis in many patients. Aurora kinases, a family of serine/threonine kinases, play a key role in regulating cell division and mitosis and are linked to tumorigenesis, metastasis, and poor prognosis in many human cancers including leukemia and lymphoma. Danusertib (Danu) is a pan-inhibitor of Aurora kinases with few data available in leukemia therapy. This study aimed to identify new molecular targets for Aurora kinase inhibition in human leukemia cells using quantitative proteomic analysis followed by verification experiments. There were at least 2932 proteins responding to Danu treatment, including AURKB, p70S6K, and RPL15, and 603 functional proteins and 245 canonical signaling pathways were involved in regulating cell proliferation, metabolism, apoptosis, and autophagy. The proteomic data suggested that Danu-regulated RPL15 signaling might contribute to the cancer cell killing effect. Our verification experiments confirmed that Danu negatively regulated AURKB/p70S6K/RPL15 axis with the involvement of PI3K/Akt/mTOR, AMPK, and p38 MAPK signaling pathways, leading to the induction of apoptosis and autophagy in human leukemia cells. Further studies are warranted to verify the feasibility via targeting AURKB/p70S6K/RPL15 axis for leukemia therapy.