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

被引:35
作者
Wu, Yao [1 ,4 ]
Peng, Ying [1 ]
Wu, Meiyan [1 ]
Zhang, Wenjing [3 ]
Zhang, Mengnan [1 ]
Xie, Ruyi [1 ]
Zhang, Pei [1 ]
Bai, Yang [1 ]
Zhao, Jinjun [2 ]
Li, Aimin [1 ]
Nan, Qingzhen [1 ]
Chen, Ye [1 ]
Ren, Yuexin [1 ]
Liu, Side [1 ]
Wang, Jide [1 ]
机构
[1] Southern Med Univ, Nanfang Hosp, Dept Gastroenterol, Guangdong Prov Key Lab Gastroenterol, Guangzhou 510515, Guangdong, Peoples R China
[2] Southern Med Univ, Nanfang Hosp, Dept Rheumatism, Guangzhou 510515, Guangdong, Peoples R China
[3] Kunming Univ Sci & Technol, Peoples Hosp Yunnan Prov 1, Dept Med Oncol, Kunming 650032, Peoples R China
[4] Nanchang Univ, Affiliated Hosp 1, Dept Gastroenterol, Nanchang 330006, Peoples R China
关键词
FOXK1; colorectal cancer; metastasis; epithelial-mesenchymal transition; invasion; BOX TRANSCRIPTION FACTORS; BREAST-CANCER; UP-REGULATION; POOR-PROGNOSIS; HEPATOCELLULAR-CARCINOMA; TUMOR PROGRESSION; BLADDER-CANCER; EXPRESSION; METASTASIS; CELLS;
D O I
10.18632/oncotarget.9457
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
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-beta 1 induced FOXK1 expression in a time-dependent pattern and the knockdown of FOXK1 inhibited TGF-beta 1-induced EMT. In vivo, higher expression of FOXK1 promotes CRC cell invasion and metastasis, and induces EMT in CRC as well. All together, 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.
引用
收藏
页码:51150 / 51162
页数:13
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