title: The metastasis suppressor, NDRG1, inhibits "stemness" of colorectal cancer via down-regulation of nuclear β-catenin and CD44.
abstract: N-myc downstream-regulated gene 1 (NDRG1), has been identified as an important metastasis suppressor for colorectal cancer (CRC). In this study, we investigated: (1) the effects of NDRG1 on CRC stemness and tumorigenesis; (2) the molecular mechanisms involved; and (3) the relationship between NDRG1 expression and colorectal cancer prognosis. Our investigation demonstrated that CRC cells with silenced NDRG1 showed more tumorigenic ability and stem cell-like properties, such as: colony and sphere formation, chemoresistance, cell invasion, high expression of CD44, and tumorigenicity in vivo. Moreover, NDRG1 silencing reduced β-catenin expression on the cell membrane, while increasing its nuclear expression. The anti-tumor activity of NDRG1 was demonstrated to be mediated by preventing β-catenin nuclear translocation, as silencing of this latter molecule could reverse the effects of silencing NDRG1 expression. NDRG1 expression was also demonstrated to be negatively correlated to CRC prognosis. In addition, there was a negative correlation between NDRG1 and nuclear β-catenin and also NDRG1 and CD44 expression in clinical CRC specimens. Taken together, our investigation demonstrates that the anti-metastatic activity of NDRG1 in CRC occurs through the down-regulation of nuclear β-catenin and suggests that NDRG1 is a significant therapeutic target.
authors.affiliation: Department of General Surgery, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200025, China.|Shanghai Minimally Invasive Surgery Center, Shanghai, 200025, China.|Molecular Pharmacology and Pathology Program, Department of Pathology and Bosch Institute, University of Sydney, Sydney, New South Wales, 2006, Australia.
authors.forename: Xiongzhi
authors.initials: X
authors.lastname: Wangpu
authors.affiliation: Department of General Surgery, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200025, China.|Shanghai Minimally Invasive Surgery Center, Shanghai, 200025, China.|Shanghai Institute of Digestive Surgery, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200025, China.
authors.forename: Xiao
authors.initials: X
authors.lastname: Yang
authors.affiliation: Department of General Surgery, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200025, China.|Shanghai Minimally Invasive Surgery Center, Shanghai, 200025, China.
authors.forename: Jingkun
authors.initials: J
authors.lastname: Zhao
authors.affiliation: Department of General Surgery, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200025, China.|Shanghai Minimally Invasive Surgery Center, Shanghai, 200025, China.
authors.forename: Jiaoyang
authors.initials: J
authors.lastname: Lu
authors.affiliation: Department of General Surgery, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200025, China.|Shanghai Institute of Digestive Surgery, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200025, China.
authors.forename: Shaopei
authors.initials: S
authors.lastname: Guan
authors.affiliation: Department of General Surgery, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200025, China.|Shanghai Minimally Invasive Surgery Center, Shanghai, 200025, China.
authors.forename: Jun
authors.initials: J
authors.lastname: Lu
authors.affiliation: Molecular Pharmacology and Pathology Program, Department of Pathology and Bosch Institute, University of Sydney, Sydney, New South Wales, 2006, Australia.
authors.forename: Zaklina
authors.initials: Z
authors.lastname: Kovacevic
authors.affiliation: Department of General Surgery, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200025, China.
authors.forename: Wensheng
authors.initials: W
authors.lastname: Liu
authors.affiliation: Department of General Surgery, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200025, China.
authors.forename: Lan
authors.initials: L
authors.lastname: Mi
authors.affiliation: Department of General Surgery, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200025, China.
authors.forename: Runsen
authors.initials: R
authors.lastname: Jin
authors.affiliation: Department of General Surgery, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200025, China.|Shanghai Minimally Invasive Surgery Center, Shanghai, 200025, China.
authors.forename: Jing
authors.initials: J
authors.lastname: Sun
authors.affiliation: Department of General Surgery, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200025, China.|Shanghai Minimally Invasive Surgery Center, Shanghai, 200025, China.
authors.forename: Fei
authors.initials: F
authors.lastname: Yue
authors.affiliation: Department of General Surgery, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200025, China.|Shanghai Minimally Invasive Surgery Center, Shanghai, 200025, China.
authors.forename: Junjun
authors.initials: J
authors.lastname: Ma
authors.affiliation: Department of General Surgery, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200025, China.|Shanghai Minimally Invasive Surgery Center, Shanghai, 200025, China.|Shanghai Institute of Digestive Surgery, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200025, China.
authors.forename: Aiguo
authors.initials: A
authors.lastname: Lu
authors.affiliation: Molecular Pharmacology and Pathology Program, Department of Pathology and Bosch Institute, University of Sydney, Sydney, New South Wales, 2006, Australia.
authors.forename: Des R
authors.initials: DR
authors.lastname: Richardson
authors.affiliation: The Division of Translational Medicine, Minhang Hospital, Fudan University, Shanghai, 201199, China.
authors.forename: Lishun
authors.initials: L
authors.lastname: Wang
authors.affiliation: Department of General Surgery, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200025, China.|Shanghai Minimally Invasive Surgery Center, Shanghai, 200025, China.|Shanghai Institute of Digestive Surgery, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200025, China.
authors.forename: Minhua
authors.initials: M
authors.lastname: Zheng
mesh_terms: D000071916:AC133 Antigen; D000368:Aged; D000818:Animals; D015703:Antigens, CD / Q000378:metabolism; D018797:Cell Cycle Proteins / Q000378:metabolism*; D045744:Cell Line, Tumor; D002462:Cell Membrane / Q000378:metabolism; D002467:Cell Nucleus / Q000378:metabolism*; D015179:Colorectal Neoplasms / Q000378:metabolism*; D015536:Down-Regulation; D005260:Female; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D020868:Gene Silencing; D006023:Glycoproteins / Q000378:metabolism; D045325:HCT116 Cells; D019073:HT29 Cells; D006801:Humans; D018960:Hyaluronan Receptors / Q000378:metabolism*; D047908:Intracellular Signaling Peptides and Proteins / Q000378:metabolism*; D008207:Lymphatic Metastasis; D008297:Male; D051379:Mice; D008819:Mice, Nude; D008875:Middle Aged; D009361:Neoplasm Invasiveness; D009362:Neoplasm Metastasis; D009368:Neoplasm Transplantation; D014411:Neoplastic Stem Cells / Q000166:cytology*; D010455:Peptides / Q000378:metabolism; D010641:Phenotype; D011379:Prognosis; D051176:beta Catenin / Q000378:metabolism*; D000099259:N-myc Downstream-Regulated Gene 1 Protein
chemical_list: D000071916:AC133 Antigen; D015703:Antigens, CD; D018797:Cell Cycle Proteins; D006023:Glycoproteins; D018960:Hyaluronan Receptors; D047908:Intracellular Signaling Peptides and Proteins; D010455:Peptides; D051176:beta Catenin; D000099259:N-myc Downstream-Regulated Gene 1 Protein; C497483:CD44 protein, human
keywords: NDRG1; colorectal cancer; stem cell-like property; tumorigenesis; β-catenin