Rab11a promotes proliferation and invasion through regulation of YAP in non-small cell lung cancer

Abstract

// Qianze Dong 1 , Lin Fu 1 , Yue Zhao 1 , Yaming Du 2 , Qingchang Li 1 , Xueshan Qiu 1 , Enhua Wang 1 1 Department of Pathology, First Affiliated Hospital and College of Basic Medical Science, China Medical University, Shenyang, China 2 Department of Cardiovascular Thoracic Surgery, The First Affiliated Hospital of Jinzhou Medical University, Jinzhou, China Correspondence to: Enhua Wang, email: wangenhuacmu@hotmail.com Keywords: Rab11a, Hippo, YAP, non-small cell lung cancer, proliferation Received: October 26, 2016      Accepted: January 09, 2017      Published: February 15, 2017 ABSTRACT Rab11a, an evolutionarily conserved Rab GTPases, plays important roles in intracellular transport and has been implicated in cancer progression. However, its role in human non-small cell lung cancer (NSCLC) has not been explored yet. In this study, we discovered that Rab11a protein was upregulated in 57/122 NSCLC tissues. Rab11a overexpression associated with advanced TNM stage, positive nodal status and poor patient prognosis. Rab11a overexpression promoted proliferation, colony formation, invasion and migration with upregulation of cyclin D1, cyclin E, and downregulation of p27 in NSCLC cell lines. Nude mice xenograft demonstrated that Rab11a promoted in vivo cancer growth. Importantly, we found that Rab11a induced YAP protein and inhibited Hippo signaling. Depletion of YAP abolished the effects of Rab11a on cell cycle proteins and cell proliferation. Furthermore, immunoprecipitation showed that Rab11a interacted with YAP in lung cancer cells. In conclusion, the present study suggestes that Rab11a serves as an important oncoprotein and a regulator of YAP in NSCLC.