title: FGF8 promotes colorectal cancer growth and metastasis by activating YAP1.
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.
authors.affiliation: State Key Laboratory of Biotherapy/Collaborative Innovation Center of Biotherapy, West China Hospital, Sichuan University, Chengdu, P. R. China.|State Key Laboratory of Oral Diseases, West China Hospital of Stomatology, Sichuan University, Chengdu, P. R. China.
authors.forename: Rui
authors.initials: R
authors.lastname: Liu
authors.affiliation: State Key Laboratory of Biotherapy/Collaborative Innovation Center of Biotherapy, West China Hospital, Sichuan University, Chengdu, P. R. China.
authors.forename: Shan
authors.initials: S
authors.lastname: Huang
authors.affiliation: Department of Biochemistry and Molecular Biology, and Molecular Medicine and Cancer Research Center, Chongqing Medical University, Chongqing, P. R. China.
authors.forename: Yunlong
authors.initials: Y
authors.lastname: Lei
authors.affiliation: The School of Biomedical Sciences, Chengdu Medical College, Chengdu, P. R. China.
authors.forename: Tao
authors.initials: T
authors.lastname: Zhang
authors.affiliation: State Key Laboratory of Biotherapy/Collaborative Innovation Center of Biotherapy, West China Hospital, Sichuan University, Chengdu, P. R. China.
authors.forename: Kui
authors.initials: K
authors.lastname: Wang
authors.affiliation: State Key Laboratory of Biotherapy/Collaborative Innovation Center of Biotherapy, West China Hospital, Sichuan University, Chengdu, P. R. China.
authors.forename: Bo
authors.initials: B
authors.lastname: Liu
authors.affiliation: Department of Biochemistry and Molecular Biology, Monash University, Clayton, Victoria, Australia.
authors.forename: Edouard C
authors.initials: EC
authors.lastname: Nice
authors.affiliation: School of Medicine, Nankai University, Tianjin, P.R. China.
authors.forename: Rong
authors.initials: R
authors.lastname: Xiang
authors.affiliation: Department of Oncology, Sichuan Provincial People's Hospital, Chengdu, P. R. China.
authors.forename: Ke
authors.initials: K
authors.lastname: Xie
authors.affiliation: The School of Biomedical Sciences, Chengdu Medical College, Chengdu, P. R. China.
authors.forename: Jingyi
authors.initials: J
authors.lastname: Li
authors.affiliation: State Key Laboratory of Biotherapy/Collaborative Innovation Center of Biotherapy, West China Hospital, Sichuan University, Chengdu, P. R. China.
authors.forename: Canhua
authors.initials: C
authors.lastname: Huang
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics* / Q000378:metabolism; D000368:Aged; D000818:Animals; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects / Q000235:genetics; D049109:Cell Proliferation / Q000187:drug effects / Q000235:genetics*; D015179:Colorectal Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D058750:Epithelial-Mesenchymal Transition / Q000235:genetics; D005260:Female; D051524:Fibroblast Growth Factor 8 / Q000235:genetics* / Q000378:metabolism / Q000494:pharmacology; D015972:Gene Expression Regulation, Neoplastic; D045325:HCT116 Cells; D006801:Humans; D007150:Immunohistochemistry; D008207:Lymphatic Metastasis; D008297:Male; D008819:Mice, Nude; D008875:Middle Aged; D010750:Phosphoproteins / Q000235:genetics* / Q000378:metabolism; D011379:Prognosis; D011485:Protein Binding; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction / Q000235:genetics; D016019:Survival Analysis; D014157:Transcription Factors; D014183:Transplantation, Heterologous; D047368:Tumor Burden / Q000235:genetics; D000091102:YAP-Signaling Proteins
chemical_list: D048868:Adaptor Proteins, Signal Transducing; C496456:FGF8 protein, human; D010750:Phosphoproteins; D014157:Transcription Factors; D000091102:YAP-Signaling Proteins; C088374:YAP1 protein, human; D051524:Fibroblast Growth Factor 8