RCC2 Interacts with Small GTPase RalA and Regulates Cell Proliferation and Motility in Gastric Cancer

• Main Authors: Wang P, Zhang W, Wang L, Liang W, Cai A, Gao Y, Chen L
• Format: Article
• Language: English
• Published: Dove Medical Press 2020-04-01
• Series: OncoTargets and Therapy
• Subjects: rcc2; rala; gastric cancer; proliferation; migration and invasion
• Online Access: https://www.dovepress.com/rcc2-interacts-with-small-gtpase-rala-and-regulates-cell-proliferation-peer-reviewed-article-OTT
• ISSN: 1178-6930

Pengpeng Wang,1,2 Wang Zhang,2 Lili Wang,2 Wenquan Liang,2 Aizhen Cai,2 Yunhe Gao,2 Lin Chen1,2 1School of Medicine, Nankai University, Tianjin 300071, People’s Republic of China; 2Department of General Surgery, Chinese People’s Liberation Army General Hospital, Beijing 100853, People’s Republic of ChinaCorrespondence: Lin ChenDepartment of General Surgery, Chinese People’s Liberation Army General Hospital, Fuxing Road 28#, Haidian District, Beijing 100853, People’s Republic of ChinaEmail [e-mail]: Regulator of chromosome condensation 2 (RCC2), also known as TD-60, is associated with various human malignant cancers. RCC2 has been shown to exhibit guanine exchange factor (GEF) activity and contribute to early mitosis. However, the role and mechanism of RCC2 in gastric cancer remain unclear.Materials and Methods: RCC2 expression in gastric cancer was studied using qPCR, Western blotting and immunochemistry staining of clinical specimens, and its roles in the cytobiology, mouse model and related molecular pathways were evaluated using gastric cell lines.Results: RCC2 was frequently overexpressed in gastric cancer. RCC2 knockdown significantly inhibited cell proliferation, migration and invasion in vitro, which was further confirmed by the RCC2 overexpression results in gastric cancer cells. Moreover, RCC2 knockdown inhibited tumor progression in vivo. Further study revealed the interaction between RCC2 and RalA. The level of RalA-GTP was decreased in gastric cancer cells after RCC2 knockdown, while an increased phosphorylation level in MAPK/JNK was found. Furthermore, the changes in the level of RalA-GTP as well as cell proliferation, migration and invasion abilities were further confirmed using RBC8, a specific small-molecule inhibitor of the intracellular actions of Ral GTPases, in gastric cancer cells.Conclusion: RCC2 plays an important role in gastric cancer. RCC2 knockdown inhibits cell growth, cell motility and tumor progression, which may act through RalA and affect the MAPK/JNK pathway.Keywords: RCC2, RalA, gastric cancer, proliferation, migration and invasion