Open AccessThe FOXK1-CCDC43 Axis Promotes the Invasion and Metastasis of Colorectal Cancer Cells
Author(s) -
Jing Wang,
Guangnan Liu,
Mengwei Liu,
Xiang Li,
Yizhi Xiao,
Huiqiong Zhu,
Xiaosheng Wu,
Ying Peng,
Wenjing Zhang,
Ping Jiang,
Aimin Li,
Qing-Zhen Nan,
Ye Chen,
Chudi Chen,
Tina Cheng,
Side Liu,
Jide Wang
Publication year - 2018
Publication title -
cellular physiology and biochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.486
H-Index - 87
eISSN - 1421-9778
pISSN - 1015-8987
DOI - 10.1159/000495924
Subject(s) - chromatin immunoprecipitation , colorectal cancer , cancer research , epithelial–mesenchymal transition , metastasis , biology , western blot , flow cytometry , zebrafish , cancer , gene expression , gene , promoter , microbiology and biotechnology , genetics
Background/Aims: The CCDC43 gene is conserved in human, rhesus monkey, mouse and zebrafish. Bioinformatics studies have demonstrated the abnormal expression of CCDC43 gene in colorectal cancer (CRC). However, the role and molecular mechanism of CCDC43 in CRC remain unknown. Methods: The functional role of CCDC43 and FOXK1 in epithelial-mesenchymal transition (EMT) was determined using immunohistochemistry, flow cytometry, western blot, EdU incorporation, luciferase, chromatin Immunoprecipitation (ChIP) and cell invasion assays. Results: The CCDC43 gene was overexpressed in human CRC. High expression of CCDC43 protein was associated with tumor progression and poor prognosis in patients with CRC. Moreover, the induction of EMT by CCDC43 occurred through TGF-β signaling. Furthermore, a positive correlation between the expression patterns of CCDC43 and FOXK1 was observed in CRC cells. Promoter assays demonstrated that FOXK1 directly bound and activated the human CCDC43 gene promoter. In addition, CCDC43 was necessary for FOXK1- mediated EMT and metastasis in vitro and vivo. Taken together, this work identified that CCDC43 promoted EMT and was a direct transcriptional target of FOXK1 in CRC cells. Conclusion: FOXK1-CCDC43 axis might be helpful to develop the drugs for the treatment of CRC.