Forkhead box Cl promotes colorectal cancer metastasis through transactivating ITGA7 and FGFR4 expression

被引：53

作者：

Liu, Jian ^{[1
,2
]}

Zhang, Zhe ^{[1
,2
]}

Li, Xiaowei ^{[1
,2
]}

Chen, Jie ^{[1
,2
]}

Wang, Guodong ^{[1
,2
]}

Tian, Zuhong ^{[1
,2
]}

Qian, Meirui ^{[1
,2
]}

Chen, Zhangqian ^{[1
,2
]}

Guo, Hao ^{[1
,2
]}

Tang, Guangbo ^{[1
,2
]}

Huang, Wenjie ^{[1
,2
,3
]}

Tian, Dean ^{[3
]}

Wang, Daowen ^{[3
]}

Nie, Yongzhan ^{[1
,2
]}

Fan, Daiming ^{[1
,2
]}

Wu, Kaichun ^{[1
,2
]}

Xia, Limin ^{[1
,2
,3
]}

机构：

[1] Fourth Mil Med Univ, Natl Clin Res Ctr Digest Dis, State Key Lab Canc Biol, Xian, Shaanxi, Peoples R China

[2] Fourth Mil Med Univ, Xijing Hosp Digest Dis, Xian, Shaanxi, Peoples R China

[3] Huazhong Univ Sci & Technol, Tongji Med Coll, Tongji Hosp, Dept Gastroenterol, Wuhan 430030, Hubei, Peoples R China

来源：

ONCOGENE | 2018年 / 37卷 / 41期

基金：

中国国家自然科学基金;

关键词：

FIBROBLAST-GROWTH-FACTOR; TO-MESENCHYMAL TRANSITION; INDICATES POOR-PROGNOSIS; TUMOR-METASTASIS; FOXC1; CARCINOMA; GENE; OVEREXPRESSION; INHIBITION; MUTATION;

D O I：

10.1038/s41388-018-0355-4

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

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 ea (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.

引用

页码：5477 / 5491

页数：15

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