Oncogene FOXK1 enhances invasion of colorectal carcinoma by inducing epithelial-mesenchymal transition

// Yao Wu 1, 4, * , Ying Peng 1, * , Meiyan Wu 1 , Wenjing Zhang 3 , Mengnan Zhang 1 , Ruyi Xie 1 , Pei Zhang 1 , Yang Bai 1 , Jinjun Zhao 2 , Aimin Li 1 , Qingzhen Nan 1 , Ye Chen 1 , Yuexin Ren 1 , Side Liu 1 , Jide Wang 1 1 Guangdong Provincial Key Laboratory of Gastroenterology, Department of Gastroenterology, Nanfang Hospital, Southern Medical University, Guangzhou, 510515, China 2 Department of Rheumatism, Nanfang Hospital, Southern Medical University, Guangzhou, 510515, China 3 Department of Medical Oncology, the First People’s Hospital of Yunnan Province, Kunming University of Science and Technology, Kunming, 650032, China 4 Department of Gastroenterology, The First Affiliated Hospital of Nanchang University, Nanchang, 330006, China * These authors contributed equally to this work Correspondence to: Side Liu, email: liuside@163.com Jide Wang, email: jidewang55@163.com Keywords: FOXK1, colorectal cancer, metastasis, epithelial-mesenchymal transition, invasion Received: July 09, 2015      Accepted: April 06, 2016      Published: May 19, 2016 ABSTRACT Transcriptional factor FOXK1 is a member of the FOX family, involved in the cell growth and metabolism. The higher expression of FOXK1 leads to a variety of diseases and may play an important role in the development of various tumors. However, the role of FOXK1 in the progression of colorectal cancer (CRC) remains unknown. We demonstrated that FOXK1 was overexpressed in 16 types of solid tumor tissues via tissue multi-array (TMA). We found that FOXK1 induced elevated expressions and transactivities of five major oncogenes in CRC. Moreover, the elevated expression of FOXK1 was showed to be correlated with tumor progression and was a significant predictor of overall survival in CRC patients. Furthermore, it was showed that the depletion of FOXK1 expression could inhibit the migratory and invasive abilities of CRC cells. In contrast, ectopic expression of FOXK1 elicited the opposite effects on these phenotypes in vitro . FOXK1 promoted tumor metastasis through EMT program induction. In addition, TGF-β1 induced FOXK1 expression in a time-dependent pattern and the knockdown of FOXK1 inhibited TGF-β1-induced EMT. In vivo , higher expression of FOXK1 promotes CRC cell invasion and metastasis, and induces EMT in CRC as well. Alltogether, it was concluded that the higher expression of FOXK1 could indicate a poor prognosis in CRC patients since that FOXK1 induces EMT and promotes CRC cell invasion in vitro and in vivo .