Department of Thoracic Surgery, First Affiliated Hospital of Fujian Medical University, Fuzhou, People's Republic of China.
Department of Pathology, First Affiliated Hospital of Fujian Medical University, Fuzhou, People's Republic of China.
Exp Cell Res. 2020 Jul 1;392(1):112002. doi: 10.1016/j.yexcr.2020.112002. Epub 2020 Apr 8.
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.
AarF 结构域激酶 5（ADCK5）是一个非典型激酶家族的成员，在许多癌症中过度表达，包括肺癌，而这种蛋白质的功能尚未阐明。在这里，我们研究了 ADCK5 参与调节肺癌细胞侵袭和迁移的机制，并表明 ADCK5 可能通过磷酸化转录因子 SOX9 来调节肿瘤癌基因人垂体肿瘤转化基因-1（PTTG1）的表达，从而增强肺癌细胞的迁移和侵袭能力。SOX9 上潜在丝氨酸磷酸化位点的突变表明丝氨酸 181 可能是维持 SOX9 转录激活以及增加 PTTG1 水平所必需的。SOX9 的丝氨酸 181 位点位于 ADCK5 的靶向基序中。ADCK5-SOX9-PTTG1 通路可能是肺癌的潜在治疗靶点。
