aarF domain containing kinase 5 gene promotes invasion and migration of lung cancer cells through ADCK5-SOX9-PTTG1 pathway.

AarF domain containing kinase 5 (ADCK5) is a member of an atypical kinase family and overexpressed in many carcinomas including lung cancer, while the function of this protein has not been elucidated. Here we investigated the mechanism of ADCK5 involved in regulating invasion and migration of lung cancer cells, and showed that ADCK5 might regulate the expression of tumor oncogene human pituitary tumor transforming gene-1 (PTTG1) by phosphorylating transcription factor SOX9, therefore enhancing the migration and invasion capabilities of lung cancer cells. Mutagenesis of potential serine phosphorylation sites on SOX9 indicated that serine 181 might be required to maintain transcription activation of SOX9 as well as increase PTTG1 levels. The serine 181 site of SOX9 is in a motif that is targeted by ADCK5. The ADCK5-SOX9-PTTG1 pathway might be a potential therapeutic target for lung cancer.