AJUBA promotes the migration and invasion of esophageal squamous cell carcinoma cells through upregulation of MMP10 and MMP13 expression

// Xuejiao Shi 1 , Zhaoli Chen 1 , Xueda Hu 1 , Mei Luo 1 , Zengmiao Sun 1 , Jiagen Li 1 , Susheng Shi 2 , Xiaoli Feng 2 , Chengcheng Zhou 1 , Zitong Li 1 , Wenhui Yang 1 , Yuan Li 1 , Pan Wang 1 , Fang Zhou 1 , Yibo Gao 1 , Jie He 1 1 Department of Thoracic Surgery, Cancer Institute and Hospital, Peking Union Medical College and Chinese Academy of Medical Sciences, Beijing, China 2 Department of Pathology, Cancer Institute and Hospital, Peking Union Medical College and Chinese Academy of Medical Sciences, Beijing, China Correspondence to: Yibo Gao, email: gaoyibo@cicams.ac.cn Jie He, email: prof.hejie@263.net Keywords: AJUBA, ERK1/2, MMP10, MMP13, ESCC Received: December 16, 2015      Accepted: April 22, 2016      Published: May 09, 2016 ABSTRACT The LIM-domain protein AJUBA has been reported to be involved in cell-cell adhesion, proliferation, migration and cell fate decision by acting as a scaffold or adaptor protein. We previously identified AJUBA as a putative cancer gene in esophageal squamous cell carcinoma (ESCC). However, the function and underlying mechanisms of AJUBA in ESCC remain largely unknown. In the present study, we detected AJUBA levels in ESCC tumor tissues and in corresponding adjacent non-tumor tissues by immunohistochemistry (IHC) and investigated the function and mechanism of AJUBA in ESCC cells. The IHC results showed that AJUBA levels were significantly higher in ESCC tissues compared with corresponding adjacent non-tumor tissues ( P < 0.001). Both in vitro and in vivo experiments showed that AJUBA promoted cell growth and colony formation, inhibited cisplatin-induced apoptosis of ESCC cells, and promoted ESCC cell migration and invasion. RNA sequencing was used to reveal the oncogenic pathways of AJUBA that were involved, and MMP10 and MMP13 were identified as two of the downstream targets of AJUBA. Thus, AJUBA upregulates the levels of MMP10 and MMP13 by activating ERK1/2. Taken together, these findings revealed that AJUBA serves as oncogenic gene in ESCC and may serve as a new target for ESCC therapy.