Palmatine attenuates MYH9 mediated nuclear localization of AURKA to induce G2/M phase arrest in colorectal cancer cells.

The mitotic kinase Aurora kinase A (AURKA), which plays a crucial role in cell cycle progression, represents a promising target for the treatment of colorectal cancer (CRC). Here, we found that AURKA is a target of a CRC suppressor, the Palmatine (PAL). However, the underlying mechanism remains elusive. This work aims to investigate the underlying mechanism how PAL suppresses CRC through AURKA. It was confirmed that AURKA played an important role in the development of CRC tumors through an Azoxymethane/Dextran sulfate sodium salt induced mice model and tissue microarrays of CRC-patients. Overexpression of AURKA was able to partially reverse the inhibitory effect of PAL on CRC cells, showing that PAL significantly inhibited the malignant phenotype and induced the G2/M phase arrest of CRC cells by down-regulating AURKA. Functional studies indicated that PAL attenuated the stability of AURKA protein and reduced its nuclear level, resulting in reduction of key proteins in the G2/M phase. Importantly, Co-IP and WB experiments suggested that Myosin heavy chain 9 (MYH9) interacted with AURKA and had an impact on its nuclear localization. PAL can decrease nuclear AURKA by reducing the interaction of AURKA and MYH9. Taken together, our study revealed that MYH9 as an auxiliary protein for the nuclear localization of AURKA and elucidated the mechanism that PAL reduced nuclear AURKA through inhibiting the interaction of AURKA and MYH9 to induce G2/M phase arrest in CRC cells. Therefore, this study may provide a theoretical basis of PAL for the treatment of CRC.