Epac1 knockdown inhibits the proliferation of ovarian cancer cells by inactivating AKT/Cyclin D1/CDK4 pathway in vitro and in vivo.
Ovarian cancer is the leading cause of death among gynecological malignancies, and high grade serous ovarian carcinoma is the most common and most aggressive subtype. Recently, it was demonstrated that cAMP mediates protein kinase A-independent effects through Epac (exchange protein directly activated by cAMP) proteins. Epac proteins, including Epac1 and Epac2, are implicated in several diverse cellular responses, such as insulin secretion, exocytosis, cellular calcium handling and formation of cell-cell junctions. Several reports document that Epac1 could play vital roles in promoting proliferation, invasion and migration of some cancer cells. However, the expression levels and roles of Epac1 in ovarian cancer have not been investigated. In the present study, we detected the expression levels of Epac1 mRNA and protein in three kinds of ovarian cancer cells SKOV3, OVCAR3 and CAOV3. Furthermore, the effect of Epac1 knockdown on the proliferation and apoptosis of SKOV3 and OVCAR3 cells was evaluated in vitro and in vivo. The results showed that there was higher expression of Epac1 mRNA and protein in SKOV3 and OVCAR3 cells. Epac1 knockdown inhibited the proliferation of SKOV3 and OVCAR3 cells in vitro and in vivo. Decreased proliferation may be due to downregulation of Epac1-induced G1 phase arrest by inactivating the AKT/Cyclin D1/CDK4 pathway, but not to alterations in the MAPK pathway or to apoptosis. Taken together, our data provide new insight into the essential role of Epac1 in regulating growth of ovarian cancer cells and suggest that Epac1 might represent an attractive therapeutic target for treatment of ovarian cancer.
Department of Immunology, Shandong University School of Medicine, 44# Wenhua Xi Road, Jinan, 250012, Shandong, People's Republic of China.
Meng
M
Gao
Department of Immunology, Shandong University School of Medicine, 44# Wenhua Xi Road, Jinan, 250012, Shandong, People's Republic of China.
Yanyan
Y
Ma
Department of Experimental Therapeutics, Division of Cancer Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
Robert C
RC
Bast
Department of Immunology, Shandong University School of Medicine, 44# Wenhua Xi Road, Jinan, 250012, Shandong, People's Republic of China.
Yue
Y
Li
Department of Immunology, Shandong University School of Medicine, 44# Wenhua Xi Road, Jinan, 250012, Shandong, People's Republic of China.
Lu
L
Wan
Department of Gynecology and Obstetrics, Jinan Central Hospital Affiliated to Shandong University, 105# Jiefang Road, Jinan, 250013, Shandong, People's Republic of China.|Department of Gynecology and Obstetrics, Shandong University School of Medicine, 44# Wenhua Xi Road, Jinan, 250012, Shandong, People's Republic of China.
Yanping
Y
Liu
Department of Gynecology and Obstetrics, Jinan Central Hospital Affiliated to Shandong University, 105# Jiefang Road, Jinan, 250013, Shandong, People's Republic of China.|Department of Gynecology and Obstetrics, Shandong University School of Medicine, 44# Wenhua Xi Road, Jinan, 250012, Shandong, People's Republic of China.
Yingshuo
Y
Sun
Department of Gynecology and Obstetrics, Jinan Central Hospital Affiliated to Shandong University, 105# Jiefang Road, Jinan, 250013, Shandong, People's Republic of China.
Zhenghui
Z
Fang
Department of Immunology, Shandong University School of Medicine, 44# Wenhua Xi Road, Jinan, 250012, Shandong, People's Republic of China.
Lining
L
Zhang
Department of Immunology, Shandong University School of Medicine, 44# Wenhua Xi Road, Jinan, 250012, Shandong, People's Republic of China. wxy990809@163.com.
Xiaoyan
X
Wang
Department of Gynecology and Obstetrics, Jinan Central Hospital Affiliated to Shandong University, 105# Jiefang Road, Jinan, 250013, Shandong, People's Republic of China. weizengtao1970@163.com.|Department of Gynecology and Obstetrics, Shandong University School of Medicine, 44# Wenhua Xi Road, Jinan, 250012, Shandong, People's Republic of China. weizengtao1970@163.com.
Zengtao
Z
Wei
D000818:Animals; D017209:Apoptosis / Q000502:physiology; D015153:Blotting, Western; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000502:physiology; D019938:Cyclin D1 / Q000378:metabolism; D051358:Cyclin-Dependent Kinase 4 / Q000378:metabolism*; D005260:Female; D055785:Gene Knockdown Techniques; D020662:Guanine Nucleotide Exchange Factors / Q000378:metabolism*; D064593:Heterografts; D006801:Humans; D007150:Immunohistochemistry; D066298:In Vitro Techniques; D051379:Mice; D008819:Mice, Nude; D010051:Ovarian Neoplasms / Q000378:metabolism / Q000473:pathology*; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D015398:Signal Transduction / Q000502:physiology*
C530104:CCND1 protein, human; D020662:Guanine Nucleotide Exchange Factors; C116122:RAPGEF3 protein, human; D019938:Cyclin D1; D051057:Proto-Oncogene Proteins c-akt; C495900:CDK4 protein, human; D051358:Cyclin-Dependent Kinase 4
Apoptosis; Cell cycle; Epac1; Ovarian cancer cells; Proliferation