Oncotarget

Research Papers:

FGF8 promotes colorectal cancer growth and metastasis by activating YAP1

Rui Liu, Shan Huang, Yunlong Lei, Tao Zhang, Kui Wang, Bo Liu, Edouard C. Nice, Rong Xiang, Ke Xie, Jingyi Li and Canhua Huang _

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Oncotarget. 2015; 6:935-952. https://doi.org/10.18632/oncotarget.2822

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Abstract

Rui Liu1,2,*, Shan Huang1,*, Yunlong Lei3,*, Tao Zhang4,*, Kui Wang1, Bo Liu1, Edouard C. Nice5, Rong Xiang6, Ke Xie7, Jingyi Li4 and Canhua Huang1

1 State Key Laboratory of Biotherapy/Collaborative Innovation Center of Biotherapy, West China Hospital, Sichuan University, Chengdu, P. R. China

2 State Key Laboratory of Oral Diseases, West China Hospital of Stomatology, Sichuan University, Chengdu, P. R. China

3 Department of Biochemistry and Molecular Biology, and Molecular Medicine and Cancer Research Center, Chongqing Medical University, Chongqing, P. R. China

4 The School of Biomedical Sciences, Chengdu Medical College, Chengdu, P. R. China

5 Department of Biochemistry and Molecular Biology, Monash University, Clayton, Victoria, Australia

6 School of Medicine, Nankai University, Tianjin, P.R. China

7 Department of Oncology, Sichuan Provincial People’s Hospital, Chengdu, P. R. China

* These authors contributed equally to this work

Correspondence:

Canhua Huang, email:

Jingyi Li, email:

Keywords: FGF8, colorectal cancer, growth, metastasis, YAP1

Received: August 26, 2014 Accepted: November 25, 2014 Published: November 26, 2014

Abstract

Colorectal cancer (CRC) is a major cause of cancer-related death worldwide. The poor prognosis of CRC is mainly due to uncontrolled tumor growth and distant metastases. In this study, we found that the level of FGF8 was elevated in the great majority of CRC cases and high FGF8 expression was significantly correlated with lymph nodes metastasis and worse overall survival. Functional studies showed that FGF8 can induce a more aggressive phenotype displaying epithelial-to-mesenchymal transition (EMT) and enhanced invasion and growth in CRC cells. Consistent with this, FGF8 can also promote tumor growth and metastasis in mouse models. Bioinformatics and pathological analysis suggested that YAP1 is a potential downstream target of FGF8 in CRC cells. Molecular validation demonstrated that FGF8 fully induced nuclear localization of YAP1 and enhanced transcriptional outcomes such as the expression of CTGF and CYR61, while decreasing YAP1 expression impeded FGF-8–induced cell growth, EMT, migration and invasion, revealing that YAP1 is required for FGF8-mediated CRC growth and metastasis. Taken together, these results demonstrate that FGF8 contributes to the proliferative and metastatic capacity of CRC cells and may represent a novel candidate for intervention in tumor growth and metastasis formation.


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