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17 February 2017 : Laboratory Research  

Forkhead Box Protein J1 (FOXJ1) is Overexpressed in Colorectal Cancer and Promotes Nuclear Translocation of β-Catenin in SW620 Cells

Kuiliang Liu1ABCDEF, Jianghao Fan1BC, Jing Wu1AEG*

DOI: 10.12659/MSM.902906

Med Sci Monit 2017; 23:856-866

Abstract

BACKGROUND: FOXJ1, which is a forkhead transcription factor, has been previously studied mostly as a ciliary transcription factor. The role of FOXJ1 in cancer progression is still elusive and controversial. In the present study, the effect of FOXJ1 in progression of colorectal cancer (CRC) was investigated.

MATERIAL AND METHODS: The pattern of FOXJ1 expression was investigated using the method of immunohistochemistry (IHC) in a tissue microarray (TMA) incorporating 50 pairs of colon cancer specimens and adjacent normal tissue. In addition, the correlation of FOXJ1 expression with clinicopathological characteristics was evaluated in the other TMA containing 208 cases of colon cancer. Moreover, the influence of regulating FOXJ1 level on the proliferation, migration, and invasion ability of colorectal cancer (CRC) cells was evaluated.

RESULTS: Increased expression of FOXJ1was significantly associated with clinical stage (p<0.05), metastasis of lymph node (p<0.05), and invasion depth (p<0.001) in colon cancer, suggesting FOXJ1 is a tumor promoter in CRC. Consistently, FOXJ1 overexpression significantly enhanced the proliferation, migration, and invasion of CRC cells, while silencing of FOXJ1 induced the opposite effect. Furthermore, up-regulation of FOXJ1 in SW620 cells markedly inhibited the level of truncated APC and the phosphorylation of β-catenin, while the level of cyclinD1 was decreased. In addition, overexpression of FOXJ1 significantly promoted nuclear translocation of b-catenin in SW620 cells.

CONCLUSIONS: These findings demonstrate that increased FOXJ1 contributes to the progression of CRC, which might be associated with the promotion effect of b-catenin nuclear translocation. FOXJ1 may be a novel therapeutic target in CRC.

Keywords: Colorectal Neoplasms, Forkhead Transcription Factors, Wnt Signaling Pathway

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Medical Science Monitor eISSN: 1643-3750
Medical Science Monitor eISSN: 1643-3750