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Interleukin enhancer-binding factor 3 and HOXC8 co-activate cadherin 11 transcription to promote breast cancer cells proliferation and migration

2017; Impact Journals LLC; Volume: 8; Issue: 64 Linguagem: Inglês

10.18632/oncotarget.22491

1949-2553

Yang Zhang, Chenchen Yang, Mingsheng Zhang, Houli Liu, Gong Chen, Jie Zhang, Shanshan Xu, Jin Zou, Yuanzhong Kai, Yong Li,

Cancer-related molecular mechanisms research

// Yang Zhang 1, * , Chenchen Yang 1, * , Mingsheng Zhang 2, * , Houli Liu 1 , Chen Gong 1 , Jie Zhang 1 , Shanshan Xu 1 , Jin Zou 1 , Yuanzhong Kai 1 and Yong Li 1 1 School of Life Sciences, Anhui University, Hefei, Anhui Province, China 2 Department of Oncology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China * These authors contributed equally to this work Correspondence to: Yong Li, email: liyongahu@163.com Keywords: CDH11; ILF3; HOXC8; transcriptional regulation; breast cancer Received: June 27, 2017 Accepted: October 28, 2017 Published: November 18, 2017 ABSTRACT Cadherin 11 (CDH11) expression is detected only in invasive breast cancer cells and aggressive breast cancer specimens. However, little is known about the molecular mechanisms of CDH11 transcriptional regulation. Here, we report that interleukin enhancer binding factor 3 (ILF3) interacts with Homeobox C8 (HOXC8) to activate CDH11 transcription in breast cancer cells. Using co-immunoprecipitation and mass spectrometry analyses, ILF3 is shown to interact with HOXC8 in breast cancer cells. We demonstrate that ILF3 binds to the CDH11 promoter on nucleotides –2982 ~ –2978 and –2602 ~ 2598 and interacts with HOXC8 to co-activate CDH11 transcription. We further show that ILF3 promotes proliferation and migration, at least partially, by facilitating CDH11 expression in breast cancer cells. Moreover, immunohistochemistry (IHC) shows that expression of CDH11, ILF3 and HOXC8 are all upregulated in breast cancer specimens compared to normal breast tissues. Importantly, the expression levels of CDH11, ILF3 and HOXC8 are elevated in the advanced stages of breast cancer, and high expression of CDH11, ILF3 and HOXC8 is associated with poor distant metastasis-free survival (DMFS) for breast cancer patients.