HNF6 promotes tumor growth in colorectal cancer and enhances liver metastasis in mouse model

被引:11
|
作者
Jiang, Kai [1 ,2 ]
Jiao, Yurong [1 ,2 ]
Liu, Yue [1 ,2 ]
Fu, Dongliang [1 ,2 ]
Geng, Haitao [3 ]
Chen, Liubo [1 ,2 ]
Chen, Haiyan [1 ,2 ]
Shen, Xiangfeng [4 ]
Sun, Lifeng [1 ]
Ding, Kefeng [1 ,2 ]
机构
[1] Zhejiang Univ, Key Lab Canc Prevent & Intervent, China Natl Minist Educ, Canc Inst,Sch Med,Affiliated Hosp 2, Hangzhou, Zhejiang, Peoples R China
[2] Zhejiang Univ, Affiliated Hosp 2, Sch Med, Dept Surg Oncol, 88 Jiefang Rd, Hangzhou 310009, Zhejiang, Peoples R China
[3] Binzhou Med Univ Hosp, Dept Oncol, Binzhou, Peoples R China
[4] Zhejiang Prov Hosp TCM, Dept Mastopathy, Hangzhou, Zhejiang, Peoples R China
基金
中国国家自然科学基金;
关键词
anoikis; colorectal cancer; HNF6; liver metastasis; tumor growth; TRANSCRIPTION FACTOR; EXPRESSION; BEHAVIOR; ANOIKIS; CELLS; RESISTANCE; MECHANISM; MATRIX;
D O I
10.1002/jcp.27140
中图分类号
Q2 [细胞生物学];
学科分类号
071009 ; 090102 ;
摘要
Hepatocyte nuclear factor 6 (HNF6), as a transcription factor, has been reported to be involved in cell proliferation, carcinogenesis, and tumor metastasis. Here, we demonstrated the role of HNF6 in tumor growth and liver metastasis in colorectal cancer (CRC). Through bioinformatics and clinical samples analysis, we found HNF6 messenger RNA was upregulated both in CRC primary sites and liver metastases, and its high expression indicated poor survival in CRC patients. In vitro studies confirmed that HNF6 promoted cell proliferation and colony formation. What is more, in mouse models, the xenografts grew significantly faster and liver metastasis rate was nearly 45% higher in mice injected with HNF6-overexpressing cells. Further mechanism exploration showed that HNF6 expression affected cell adhesion and conferred resistance to anoikis in CRC cells. Taken together, HNF6 expression was upregulated in CRC and closely correlated with poor survival. HNF6 promoted CRC cell proliferation and tumor growth, and may contribute to liver metastasis via conferring cell resistance to anoikis.
引用
收藏
页码:3675 / 3684
页数:10
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