title: C-kit signaling promotes proliferation and invasion of colorectal mucinous adenocarcinoma in a murine model.
abstract: It was reported that the receptor tyrosine kinase (RTK) family often highly expressed in several mucinous carcinomas. In the present study, we established a murine model of colorectal mucinous adenocardinoma (CRMAC) by treating C57 mice [both wild type (WT) and loss-of-function c-kit mutant type (Wads-/-)] with AOM+DSS for 37 weeks and found that c-kit, a member of RTK family, clearly enhanced the tumor cell proliferation by decreasing p53 and increasing cyclin D1 through AKT pathway. Significantly, c-kit strongly promoted tumor cell invasiveness by increasing ETV4, which induced MMP7 expression and epithelial-mesenchymal transition (EMT) via ERK pathway. In vitro up- or down-regulating c-kit activation in human colorectal cancer HCT-116 cells further consolidated these results. In conclusion, our data suggested that the c-kit signaling obviously promoted proliferation and invasion of CRMAC. Therefore, targeting the c-kit signaling and its downstream molecules might provide the potential strategies for treatment of patients suffering from CRMAC in the future.
authors.affiliation: Department of Histology and Embryology, School of Basic Medical Sciences, Capital Medical University, Beijing 100069, P. R. China.|Beijing Key Laboratory of Cancer Invasion and Metastasis Research, Beijing 100069, P. R. China.
authors.forename: Jun
authors.initials: J
authors.lastname: Tan
authors.affiliation: Department of Histology and Embryology, School of Basic Medical Sciences, Capital Medical University, Beijing 100069, P. R. China.|Beijing Key Laboratory of Cancer Invasion and Metastasis Research, Beijing 100069, P. R. China.|Cancer Institute of Capital Medical University, Beijing 100069, P. R. China.
authors.forename: Shu
authors.initials: S
authors.lastname: Yang
authors.affiliation: Department of Histology and Embryology, School of Basic Medical Sciences, Capital Medical University, Beijing 100069, P. R. China.|Cancer Institute of Capital Medical University, Beijing 100069, P. R. China.
authors.forename: Ping
authors.initials: P
authors.lastname: Shen
authors.affiliation: Department of Histology and Embryology, School of Basic Medical Sciences, Capital Medical University, Beijing 100069, P. R. China.|Beijing Key Laboratory of Cancer Invasion and Metastasis Research, Beijing 100069, P. R. China.|Cancer Institute of Capital Medical University, Beijing 100069, P. R. China.
authors.forename: Haimei
authors.initials: H
authors.lastname: Sun
authors.affiliation: Department of Histology and Embryology, School of Basic Medical Sciences, Capital Medical University, Beijing 100069, P. R. China.|Cancer Institute of Capital Medical University, Beijing 100069, P. R. China.
authors.forename: Jie
authors.initials: J
authors.lastname: Xiao
authors.affiliation: Department of Histology and Embryology, School of Basic Medical Sciences, Capital Medical University, Beijing 100069, P. R. China.|Beijing Key Laboratory of Cancer Invasion and Metastasis Research, Beijing 100069, P. R. China.
authors.forename: Yaxi
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Department of Histology and Embryology, School of Basic Medical Sciences, Capital Medical University, Beijing 100069, P. R. China.|Beijing Key Laboratory of Cancer Invasion and Metastasis Research, Beijing 100069, P. R. China.|Cancer Institute of Capital Medical University, Beijing 100069, P. R. China.
authors.forename: Bo
authors.initials: B
authors.lastname: Wu
authors.affiliation: Department of Histology and Embryology, School of Basic Medical Sciences, Capital Medical University, Beijing 100069, P. R. China.|Beijing Key Laboratory of Cancer Invasion and Metastasis Research, Beijing 100069, P. R. China.|Cancer Institute of Capital Medical University, Beijing 100069, P. R. China.
authors.forename: Fengqing
authors.initials: F
authors.lastname: Ji
authors.affiliation: Department of Histology and Embryology, School of Basic Medical Sciences, Capital Medical University, Beijing 100069, P. R. China.
authors.forename: Jihong
authors.initials: J
authors.lastname: Yan
authors.affiliation: Department of Histology and Embryology, School of Basic Medical Sciences, Capital Medical University, Beijing 100069, P. R. China.
authors.forename: Hong
authors.initials: H
authors.lastname: Xue
authors.affiliation: Department of Histology and Embryology, School of Basic Medical Sciences, Capital Medical University, Beijing 100069, P. R. China.|Beijing Key Laboratory of Cancer Invasion and Metastasis Research, Beijing 100069, P. R. China.|Cancer Institute of Capital Medical University, Beijing 100069, P. R. China.
authors.forename: Deshan
authors.initials: D
authors.lastname: Zhou
mesh_terms: D000230:Adenocarcinoma / Q000235:genetics; D002288:Adenocarcinoma, Mucinous / Q000378:metabolism*; D000818:Animals; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D015179:Colorectal Neoplasms / Q000378:metabolism*; D019938:Cyclin D1 / Q000378:metabolism; D004195:Disease Models, Animal; D058750:Epithelial-Mesenchymal Transition; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism; D015972:Gene Expression Regulation, Neoplastic; D005838:Genotype; D045325:HCT116 Cells; D006801:Humans; D016086:Lentivirus / Q000235:genetics; D020783:Matrix Metalloproteinase 7 / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D009361:Neoplasm Invasiveness; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D019009:Proto-Oncogene Proteins c-kit / Q000378:metabolism*; D015398:Signal Transduction; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism
chemical_list: C530104:CCND1 protein, human; C530105:Ccnd1 protein, mouse; C495901:TP53 protein, human; D016159:Tumor Suppressor Protein p53; D019938:Cyclin D1; D019009:Proto-Oncogene Proteins c-kit; C494918:AKT1 protein, human; C514862:Akt1 protein, mouse; D051057:Proto-Oncogene Proteins c-akt; D048049:Extracellular Signal-Regulated MAP Kinases; C060932:MMP7 protein, human; D020783:Matrix Metalloproteinase 7
keywords: C-kit; ETV4; colorectal mucinous adenocarcinoma; murine model