TLE4 promotes colorectal cancer progression through activation of JNK/c-Jun signaling pathway

// Shu-Yang Wang 1, 2, 3, * , Ke Gao 1, 2, 3, 4, * , Dan-Ling Deng 1, 2, 3 , Juan-Juan Cai 1, 2, 3 , Zhi-Yuan Xiao 1, 2, 3 , Liu-Qing He 1, 2, 3 , Hong-Li Jiao 1, 2, 3 , Ya-Ping Ye 1, 2, 3 , Run-Wei Yang 1, 2, 3 , Ting-Ting Li 1, 2, 3 , Li Liang 1, 2, 3 , Wen-Ting Liao 1, 2, 3 , Yan-Qing Ding 1, 2, 3 1 Department of Pathology, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong, China 2 Department of Pathology, School of Basic Medical Sciences, Southern Medical University, Guangzhou, Guangdong, China 3 State Key Laboratory of Oncology in Southern China, Department of Experimental, Guangzhou, Guangdong, China 4 Department of Pathology, The Fifth Affiliated Hospital of Southern Medical University, Guangzhou, Guangdong, China * These authors contributed equally to this work Correspondence to: Yan-Qing Ding, e-mail: dyq@fimmu.com Wen-Ting Liao, e-mail: liaowt2002@gmail.com Keywords: TLE4, colorectal cancer, JNK, c-Jun, proliferation Received: August 05, 2015      Accepted: November 21, 2015      Published: December 20, 2015 ABSTRACT The Groucho transcriptional co-repressor TLE4 protein has been shown to be a tumor suppressor in a subset of acute myeloid leukemia. However, little is known about its role in development and progression of solid tumor. In this study, we found that the expression of TLE4 in colorectal cancer (CRC) tissues was significantly higher than that in their matched adjacent intestine epithelial tissues. In addition, high expression of TLE4 was significantly correlated with advanced Dukes stage, lymph node metastasis and poor prognosis of CRC. Moreover, enforced expression of TLE4 in CRC cell lines significantly enhanced proliferation, invasion and tumor growth. On the contrary, knock down of TLE4 repressed cell proliferation, invasion and tumor growth. Furthermore, our study exhibited that the TLE4 promoted cell proliferation and invasion partially via activation of JNK-c-Jun pathway and subsequently increased cyclinD1 and decreased P27Kip1 expression. In conclusion, these results suggested that TLE4, a potential prognostic biomarker for CRC, plays an important role in the development and progression of human CRC.