OncoTargets and Therapy (May 2020)
Overexpression of GAS6 Promotes Cell Proliferation and Invasion in Bladder Cancer by Activation of the PI3K/AKT Pathway
Abstract
Shiyu Mao,1 Yuan Wu,2 Ruiliang Wang,1 Yadong Guo,1 Dexi Bi,3 Wenchao Ma,2 Wentao Zhang,1 Junfeng Zhang,1,* Yang Yan,1 Xudong Yao1,* 1Department of Urology, Shanghai Tenth People’s Hospital, Tongji University School of Medicine, Shanghai 200072, People’s Republic of China; 2Department of Urology, Shanghai Tenth People’s Hospital, Anhui Medical University, Hefei 230032, People’s Republic of China; 3Department of Pathology, Shanghai Tenth People’s Hospital, Tongji University School of Medicine, Shanghai 200072, People’s Republic of China*These authors contributed equally to this workCorrespondence: Junfeng Zhang; Xudong YaoDepartment of Urology, Shanghai Tenth People’s Hospital, Tongji University School of Medicine, Shanghai 200072, People’s Republic of ChinaTel +8613817811836Fax +86-21-66305158Email [email protected]; [email protected]: Growth arrest-specific 6 (GAS6) is a secreted vitamin K-dependent protein abnormally expressed in various human tumor tissues and can activate the receptor Tyro3, Axl, and Mer to promote cancer cell proliferation and invasion. Until now, the role of GAS6 has been poorly understood in bladder cancer (BCa).Materials and Methods: Using bioinformatics analysis, we screened genes significantly associated with overall survival in BCa. The association between GAS6 and survival was evaluated by tissue microarray and IHC staining. We investigated the effect of GAS6 on the development of BCa through in vitro and in vivo experiments.Results: Here, we report that GAS6 is highly expressed in bladder cancer and is significantly associated with tumor grade, T stage, and worse prognosis. We found that GAS6 depletion inhibited proliferation, migration, and invasion of BCa cells. In addition, bioinformatics analysis revealed that GAS6 may be involved in the regulation of PI3K-AKT signaling pathway by binding to receptor TAM and has a significant positive correlation with PI3K family gene expression. Furthermore, Western blot experiments have shown that GAS6 might modulate the PI3K-AKT signaling to regulate proliferation and invasion of BCa cells. Treatment of BCa cells with SC79, an AKT activator, partially restored the effect of GAS6 silencing on cell proliferation and invasion.Conclusion: The present study suggests that GAS6 may play a pivotal role in the development of BCa and may be a potential target for its treatment.Keywords: bladder cancer, GAS6, proliferation, invasion, PI3K/AKT
