| Literature DB >> 29884889 |
Jian Liu1, Zhe Zhang1, Xiaowei Li1, Jie Chen1, Guodong Wang1, Zuhong Tian1, Meirui Qian1, Zhangqian Chen1, Hao Guo1, Guangbo Tang1, Wenjie Huang1,2, Dean Tian2, Daowen Wang2, Yongzhan Nie1, Daiming Fan1, Kaichun Wu3, Limin Xia4,5.
Abstract
Metastatic colorectal cancer (CRC) is one of the most common causes of cancer death worldwide; however, the molecular mechanism underlying CRC metastasis remains unknown. Using an integrated approach, we identified forkhead box C1 (FOXC1) as a novel regulator of CRC metastasis. Elevated expression of FOXC1 is significantly correlated with metastasis, recurrence and reduced survival. FOXC1 overexpression promotes CRC invasion and lung metastasis, whereas FOXC1 knockdown has the opposite effect. In addition, FOXC1 directly binds its target genes integrin α7 (ITGA7) and fibroblast growth factor receptor 4 (FGFR4) and activates their expression. Genetic epistasis analysis confirmed that ITGA7 and FGFR4 act downstream of FOXC1. Furthermore, pharmaceutical inhibition of FGFR4 can reverse CRC metastasis mediated by FOXC1 overexpression. These results suggest that FOXC1 is a prognostic biomarker in CRC patients and targeting the FGFR4 signaling pathway may provide a promising strategy for the treatment of FOXC1-driven CRC metastasis.Entities:
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Year: 2018 PMID： 29884889 DOI： 10.1038/s41388-018-0355-4
Source DB: PubMed Journal: Oncogene ISSN： 0950-9232 Impact factor: 9.867