J Cancer 2019; 10(18):4178-4188. doi:10.7150/jca.34430
Androgen Receptor Promotes Gastric Carcinogenesis via Upregulating Cell Cycle-Related Kinase Expression
1. State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-Sen University Cancer Center, Guangzhou, Guangdong, China
2. Endoscopy Center, Inner Mongolia key laboratory of endoscopic digestive diseases, Inner Mongolia People's Hospital, Hohhot, Inner Mongolia Autonomous Region, China
* These authors have equally contributed to this work.
Gastric cancer (GC) is a leading global health problem as it is the fifth most common cancer type and the third most common cause of cancer-related deaths worldwide. In most areas of the world, the incidence rate of GC is 1.5- to 3-fold higher in males than in females. The androgen receptor (AR) is an independent adverse prognostic factor in patients with GC. However, the mechanism by which AR regulates the progression of GC remains unclear. In this study, we found that AR expression was upregulated in 6/8 GC cell lines, and this expression was higher than that in immortalized gastric cells. AR expression was also higher in GC tissues than in adjacent tissues. Moreover, the ectopic expression of AR promoted the colony formation ability, migration and invasion of GC cells. In contrast, AR knockdown had the opposite effects on GC cell lines. Remarkably, we found that AR regulated cell cycle-related kinase (CCRK) expression through transcriptional mechanisms. The AR-CCRK axis promoted GC development through the phosphorylation of GSK3β and β-catenin. Furthermore, TCGA data revealed that high expression of AR or CCRK was related to poor prognosis in GC patients. The prognosis was significantly worse in patients with concurrent high AR and CCRK expression than in patients with low AR and CCRK expression. In conclusion, our study demonstrated that AR and CCRK acted as oncogenes in GC progression. However, their clinical roles require further exploration.
Keywords: AR, CCRK, gastric cancer, prognosis
Wang R, Xu Xy, Zhu H, Liang X, Li X, Jia Mx, Wang Qh, Wang Hy, Li Xx, Zhao Gj. Androgen Receptor Promotes Gastric Carcinogenesis via Upregulating Cell Cycle-Related Kinase Expression. J Cancer 2019; 10(18):4178-4188. doi:10.7150/jca.34430. Available from http://www.jcancer.org/v10p4178.htm