5-Azacytidine promotes invadopodia formation and tumor metastasis through the upregulation of PI3K in ovarian cancer cells
Metrics: PDF 1547 views | HTML 2353 views | ?
Dan Cao1,*, Dan Li1,*, Yong Huang1, Yu Ma1,2, Binglan Zhang1, Chengjian Zhao1, Senyi Deng1, Min Luo1, Tao Yin1, Yu-Quan Wei1 and Wei Wang1
1Department of Abdominal Oncology, Cancer Center and State Key Laboratory of Biotherapy, Collaborative Innovation Center for Biotherapy, West China Hospital, Sichuan University, Chengdu, Sichuan, China
2Department of Gynecology, West China Second Hospital, Sichuan University, Chengdu, Sichuan, China
*These authors contributed equally to this work
Wei Wang, email: [email protected]
Keywords: 5-Azacytidine, methylation, invadopodia, metastasis, ovarian cancer
Received: June 29, 2016 Accepted: May 09, 2017 Published: June 20, 2017
The high incidence of metastasis accounts for most of the lethality of ovarian cancer. Invadopodia are small, specialized types of machinery that degrade the extracellular matrix and are thus involved in the invasion and metastasis of cancer cells. The formation of invadopodia is regulated by both genetic and epigenetic factors. However, the ways by which methylation/demethylation regulates the dynamics of invadopodia in ovarian cancer are largely unknown. In this study, we found that the inhibition of methylation by 5-AZ (5-Azacytidine) increased the formation of invadopodia and enhanced degradation of the extracellular matrix in ovarian cancer cells. In mouse xenograft models, treatment with 5-AZ increased the number of metastatic nodules, which suggests an elevated potential for metastasis by demethylation. Further investigation indicated that the inhibition of methylation elevated the transcription of PIK3CA and upregulated genes involved in the PI3K-AKT signaling pathway. In addition, this induction likely occurs though the epigenetic regulation of PIK3CA because analyses of the DNA methylation level of the PIK3CA promoter region found that 5-AZ treatment decreased the methylation of CpG islands in SKOV3 and A2780 cells. Our study demonstrated that epigenetic factors regulate the metastatic potential of ovarian cancer cells and provide rationale for therapies that inhibit PI3K- invadopodia-mediated metastasis.
All site content, except where otherwise noted, is licensed under a Creative Commons Attribution 4.0 License.