title: The metastatic suppressor NDRG1 inhibits EMT, migration and invasion through interaction and promotion of caveolin-1 ubiquitylation in human colorectal cancer cells.
abstract: N-myc downstream-regulated gene 1 (NDRG1) has been reported to act as a key regulatory molecule in tumor progression-related signaling pathways, especially in tumor metastasis. However, the related mechanism has not been fully discovered yet. Herein we demonstrated that the novel molecule of cell migration and invasion, caveolin-1, has direct interaction with NDRG1 in human colorectal cancer (CRC) cells. Moreover, we discovered that NDRG1 reduces caveolin-1 protein expression through promoting its ubiquitylation and subsequent degradation via the proteasome in CRC cells. In addition, caveolin-1 mediates the suppressive function of NDRG1 in epithelial-mesenchymal transition, migration and invasion in vitro and metastasis in vivo. These results help to fulfill the potential mechanisms of NDRG1 in anti-metastatic treatment for human colorectal cancer.
authors.affiliation: Department of General Surgery, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.|Shanghai Minimally Invasive Surgery Center, Shanghai, China.|Department of Gastrointestinal Surgery, Peking University Cancer Hospital and Institute, Beijing, China.|Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Division of Gastrointestinal Cancer Translational Research Laboratory, Peking University Cancer Hospital and Institute, Beijing, China.
authors.forename: L
authors.initials: L
authors.lastname: Mi
authors.affiliation: Department of General Surgery, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.|Shanghai Minimally Invasive Surgery Center, Shanghai, China.
authors.forename: F
authors.initials: F
authors.lastname: Zhu
authors.affiliation: Department of General Surgery, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.|Shanghai Minimally Invasive Surgery Center, Shanghai, China.
authors.forename: X
authors.initials: X
authors.lastname: Yang
authors.affiliation: Department of General Surgery, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.|Shanghai Minimally Invasive Surgery Center, Shanghai, China.
authors.forename: J
authors.initials: J
authors.lastname: Lu
authors.affiliation: Key Laboratory of Cell Differentiation and Apoptosis of Chinese Ministry of Education, Department of Pathophysiology, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
authors.forename: Y
authors.initials: Y
authors.lastname: Zheng
authors.affiliation: Key Laboratory of Cell Differentiation and Apoptosis of Chinese Ministry of Education, Department of Pathophysiology, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
authors.forename: Q
authors.initials: Q
authors.lastname: Zhao
authors.affiliation: Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Division of Gastrointestinal Cancer Translational Research Laboratory, Peking University Cancer Hospital and Institute, Beijing, China.
authors.forename: X
authors.initials: X
authors.lastname: Wen
authors.affiliation: Department of General Surgery, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.|Shanghai Minimally Invasive Surgery Center, Shanghai, China.
authors.forename: A
authors.initials: A
authors.lastname: Lu
authors.affiliation: Department of General Surgery, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.|Shanghai Minimally Invasive Surgery Center, Shanghai, China.
authors.forename: M
authors.initials: M
authors.lastname: Wang
authors.affiliation: Department of General Surgery, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.|Shanghai Minimally Invasive Surgery Center, Shanghai, China.
authors.forename: M
authors.initials: M
authors.lastname: Zheng
authors.affiliation: Department of Gastrointestinal Surgery, Peking University Cancer Hospital and Institute, Beijing, China.|Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Division of Gastrointestinal Cancer Translational Research Laboratory, Peking University Cancer Hospital and Institute, Beijing, China.
authors.forename: J
authors.initials: J
authors.lastname: Ji
authors.affiliation: Department of General Surgery, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.|Shanghai Minimally Invasive Surgery Center, Shanghai, China.
authors.forename: J
authors.initials: J
authors.lastname: Sun
mesh_terms: D000818:Animals; D051242:Caveolin 1 / Q000378:metabolism*; D018797:Cell Cycle Proteins / Q000378:metabolism*; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000502:physiology; D015179:Colorectal Neoplasms / Q000378:metabolism / Q000473:pathology*; D058750:Epithelial-Mesenchymal Transition / Q000502:physiology*; D005455:Fluorescent Antibody Technique; D015972:Gene Expression Regulation, Neoplastic; D064593:Heterografts; D006801:Humans; D015151:Immunoblotting; D007150:Immunohistochemistry; D047468:Immunoprecipitation; D047908:Intracellular Signaling Peptides and Proteins / Q000378:metabolism*; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D009361:Neoplasm Invasiveness / Q000473:pathology; D060888:Real-Time Polymerase Chain Reaction; D054875:Ubiquitination; D000099259:N-myc Downstream-Regulated Gene 1 Protein
chemical_list: D051242:Caveolin 1; D018797:Cell Cycle Proteins; D047908:Intracellular Signaling Peptides and Proteins; D000099259:N-myc Downstream-Regulated Gene 1 Protein; C495540:CAV1 protein, human