title: FOXD3 is a tumor suppressor of colon cancer by inhibiting EGFR-Ras-Raf-MEK-ERK signal pathway.
abstract: Forkhead box D3 (FOXD3), as a transcriptional repressor, is well known to be involved in the regulation of development. Although FoxD3 is associated with several cancers, its role in colon cancer and the underlying mechanism are still unclear. Here, we first showed that FOXD3 knockdown dramatically increased the proliferation of human colon cancer cells, enhanced cell invasive ability and inhibited cell apoptosis. In vivo xenograft studies confirmed that the FOXD3-knockdown cells were more tumorigenic than the controls. Silencing FOXD3 markedly activated EGFR/Ras/Raf/MEK/ERK pathway in human colon cancer cells. In addition, blocking EGFR effectively decreased the activity of MAPK induced by FOXD3 knockdown. In human cancer tissue, the expression of FOXD3 was reduced, however, the EGFR/Ras/Raf/MEK/ERK pathway was activated. Our study indicates that FOXD3 may play a protective role in human colon formation by regulating EGFR/Ras/Raf/MEK/ERK signal pathway. It is proposed that FOXD3 may have potential as a new therapeutic target in human colon cancer treatment.
authors.affiliation: Department of Biochemistry and Molecular Biology, Guangxi Medical University, Nanning, Guangxi, China.|National Center for International Research of Biological Targeting Diagnosis and Therapy, Guangxi Key Laboratory of Biological Targeting Diagnosis and Therapy Research, Guangxi Medical University, Nanning, Guangxi, China.|Shanghai Key Laboratory of Regulatory Biology, Institute of Biomedical Sciences, School of Life Sciences, East China Normal University, Shanghai, China.
authors.forename: Kun
authors.initials: K
authors.lastname: Li
authors.affiliation: Department of Orthopedics, Changzheng Hospital, The Second Military Medical University, Shanghai, People's Republic of China.
authors.forename: Qunfeng
authors.initials: Q
authors.lastname: Guo
authors.affiliation: Department of Orthopedics, Changzheng Hospital, The Second Military Medical University, Shanghai, People's Republic of China.
authors.forename: Jun
authors.initials: J
authors.lastname: Yang
authors.affiliation: Shanghai Key Laboratory of Regulatory Biology, Institute of Biomedical Sciences, School of Life Sciences, East China Normal University, Shanghai, China.
authors.forename: Hui
authors.initials: H
authors.lastname: Chen
authors.affiliation: Shanghai Key Laboratory of Regulatory Biology, Institute of Biomedical Sciences, School of Life Sciences, East China Normal University, 500 Dongchuan Road, Shanghai, China.
authors.forename: Kewen
authors.initials: K
authors.lastname: Hu
authors.affiliation: Department of Biochemistry and Molecular Biology, Guangxi Medical University, Nanning, Guangxi, China.|National Center for International Research of Biological Targeting Diagnosis and Therapy, Guangxi Key Laboratory of Biological Targeting Diagnosis and Therapy Research, Guangxi Medical University, Nanning, Guangxi, China.
authors.forename: Juan
authors.initials: J
authors.lastname: Zhao
authors.affiliation: Department of Biochemistry and Molecular Biology, Guangxi Medical University, Nanning, Guangxi, China.|National Center for International Research of Biological Targeting Diagnosis and Therapy, Guangxi Key Laboratory of Biological Targeting Diagnosis and Therapy Research, Guangxi Medical University, Nanning, Guangxi, China.
authors.forename: Shunxin
authors.initials: S
authors.lastname: Zheng
authors.affiliation: Shanghai Key Laboratory of Regulatory Biology, Institute of Biomedical Sciences, School of Life Sciences, East China Normal University, Shanghai, China.
authors.forename: Xiufeng
authors.initials: X
authors.lastname: Pang
authors.affiliation: Department of Biochemistry and Molecular Biology, Guangxi Medical University, Nanning, Guangxi, China.|National Center for International Research of Biological Targeting Diagnosis and Therapy, Guangxi Key Laboratory of Biological Targeting Diagnosis and Therapy Research, Guangxi Medical University, Nanning, Guangxi, China.
authors.forename: Sufang
authors.initials: S
authors.lastname: Zhou
authors.affiliation: Shanghai Key Laboratory of Regulatory Biology, Institute of Biomedical Sciences, School of Life Sciences, East China Normal University, Shanghai, China.
authors.forename: Yongyan
authors.initials: Y
authors.lastname: Dang
authors.affiliation: Shanghai Key Laboratory of Regulatory Biology, Institute of Biomedical Sciences, School of Life Sciences, East China Normal University, Shanghai, China.
authors.forename: Lei
authors.initials: L
authors.lastname: Li
mesh_terms: D000818:Animals; D018938:Caco-2 Cells; D049109:Cell Proliferation; D003110:Colonic Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D015536:Down-Regulation; D066246:ErbB Receptors / Q000378:metabolism; D005260:Female; D051858:Forkhead Transcription Factors / Q000235:genetics* / Q000378:metabolism*; D015972:Gene Expression Regulation, Neoplastic; D045325:HCT116 Cells; D006801:Humans; D020935:MAP Kinase Signaling System; D051379:Mice; D020929:Mitogen-Activated Protein Kinase Kinases / Q000378:metabolism; D009368:Neoplasm Transplantation; D048490:raf Kinases / Q000378:metabolism; D018631:ras Proteins / Q000378:metabolism
chemical_list: C503514:FOXD3 protein, human; D051858:Forkhead Transcription Factors; C512478:EGFR protein, human; D066246:ErbB Receptors; D048490:raf Kinases; D020929:Mitogen-Activated Protein Kinase Kinases; D018631:ras Proteins
keywords: EGFR; FOXD3; Ras/Raf/MEK/ERK signal pathway; colon cancer