The metastasis suppressor, NDRG1, inhibits “stemness” of colorectal cancer via down-regulation of nuclear β-catenin and CD44

Cell Nucleus 0301 basic medicine Gene Expression Profiling Cell Membrane Intracellular Signaling Peptides and Proteins Down-Regulation Cell Cycle Proteins HCT116 Cells 3. Good health Gene Expression Regulation, Neoplastic 03 medical and health sciences Hyaluronan Receptors Antigens, CD Cell Line, Tumor Animals Humans Female AC133 Antigen Gene Silencing Colorectal Neoplasms HT29 Cells Aged Glycoproteins
DOI: 10.18632/oncotarget.5294 Publication Date: 2015-09-29T21:54:23Z
ABSTRACT
// Xiongzhi Wangpu 1, 2, 3 , Xiao Yang 4 Jingkun Zhao 2 Jiaoyang Lu Shaopei Guan Jun Zaklina Kovacevic Wensheng Liu 1 Lan Mi Runsen Jin Jing Sun Fei Yue Junjun Ma Aiguo Des R. Richardson Lishun Wang 5 Minhua Zheng Department of General Surgery, Ruijin Hospital, Shanghai Jiao Tong University School Medicine, Shanghai, 200025, China Minimally Invasive Surgery Center, Molecular Pharmacology and Pathology Program, Bosch Institute, Sydney, New South Wales, 2006, Australia Institute Digestive The Division Translational Minhang Fudan University, 201199, Correspondence to: Zheng, e-mail: wangpuxz@hotmail.com Wang, lishunwang@fudan.edu.cn Richardson, d.richardson@med.usyd.edu.au Keywords: β-catenin, colorectal cancer, NDRG1, stem cell-like property, tumorigenesis Received: March 18, 2015 Accepted: September 04, Published: ABSTRACT N-myc downstream-regulated gene (NDRG1), has been identified as an important metastasis suppressor for cancer (CRC). In this study, we investigated: (1) the effects NDRG1 on CRC stemness tumorigenesis; (2) molecular mechanisms involved; (3) relationship between expression prognosis. Our investigation demonstrated that cells with silenced showed more tumorigenic ability properties, such as: colony sphere formation, chemoresistance, cell invasion, high CD44, tumorigenicity in vivo . Moreover, silencing reduced β-catenin membrane, while increasing its nuclear expression. anti-tumor activity was to be mediated by preventing translocation, latter molecule could reverse also negatively correlated addition, there a negative correlation CD44 clinical specimens. Taken together, our demonstrates anti-metastatic occurs through down-regulation suggests is significant therapeutic target.
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