title: Knockdown of NDRG1 promote epithelial-mesenchymal transition of colorectal cancer via NF-κB signaling.
abstract: BACKGROUND
  NDRG1 plays important roles in tumor growth and metastasis of colorectal cancer (CRC). The relation between NDRG1 and metastatic colorectal cancer (mCRC) has not been identified and the mechanism of NDRG1 involving in mCRC needs to be elucidated.
  
  
  METHODS
  Correlations between NDRG1 and clinicopathological characteristics and prognosis of 164 patients with mCRC were evaluated. Sensitivity of NDRG1-knockdown colon cancer cell to irinotecan (CPT-11) was determined by MTT assay. Blocking of NF-κB signaling by p65 siRNA interference was carried out to explore the mechanism of NDRG1 involving in epithelial-mesenchymal transition (EMT)-regulated invasion and metastasis of CRC.
  
  
  RESULTS
  NDRG1 expression was significantly negatively correlated with differentiation (P = 0.008) and lymph node metastasis (P = 0.016) of mCRC. NDRG1 was a favorable prognostic factor of mCRC, although might be responsible for CPT-11 resistance in vitro. Knockdown of NDRG1 promoted EMT of CRC cells via NF-κB signaling. Depletion of NDRG1 increased phosphorylation level of NF-κB. E-cadherin expression was increased and Vimentin expression was reduced in the p65-siRNA treated group, compared with the control group (P < 0.001).
  
  
  CONCLUSIONS
  NDRG1 appears to prevent EMT-induced metastasis by attenuating NF-κB signaling in mCRC. NDRG1 may be an independent prognostic factor for good survival of mCRC. J. Surg. Oncol. 2016;114:520-527. © 2016 Wiley Periodicals, Inc.
authors.affiliation: Department of Oncology, Xiangya Hospital, Central South University, Changsha, Hunan, China.
authors.forename: Junli
authors.initials: J
authors.lastname: Ma
authors.affiliation: Department of Biochemistry, Cancer Hospital of Henan Province, The Affiliated Cancer Hospital of Zhengzhou University, Henan, China.
authors.forename: Quanli
authors.initials: Q
authors.lastname: Gao
authors.affiliation: Department of Oncology, Xiangya Hospital, Central South University, Changsha, Hunan, China.|Institute of Medical Sciences, Xiangya Hospital, Central South University, Changsha, Hunan, China.|Key Laboratory for Molecular Radiation Oncology of Hunan Province, Xiangya Hospital, Central South University, Changsha, Hunan, China.
authors.forename: Shan
authors.initials: S
authors.lastname: Zeng
authors.affiliation: Institute of Medical Sciences, Xiangya Hospital, Central South University, Changsha, Hunan, China.|Key Laboratory for Molecular Radiation Oncology of Hunan Province, Xiangya Hospital, Central South University, Changsha, Hunan, China.
authors.forename: Hong
authors.initials: H
authors.lastname: Shen
mesh_terms: D000328:Adult; D000368:Aged; D002166:Camptothecin / Q000031:analogs & derivatives / Q000494:pharmacology; D018797:Cell Cycle Proteins / Q000235:genetics / Q000502:physiology*; D015179:Colorectal Neoplasms / Q000188:drug therapy / Q000401:mortality / Q000473:pathology*; D058750:Epithelial-Mesenchymal Transition; D005260:Female; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics / Q000502:physiology*; D000077146:Irinotecan; D008207:Lymphatic Metastasis; D008297:Male; D008875:Middle Aged; D016328:NF-kappa B / Q000502:physiology*; D015398:Signal Transduction / Q000502:physiology*; D014746:Vimentin / Q000032:analysis; D000099259:N-myc Downstream-Regulated Gene 1 Protein
chemical_list: D002166:Camptothecin; D018797:Cell Cycle Proteins; D047908:Intracellular Signaling Peptides and Proteins; D000077146:Irinotecan; D016328:NF-kappa B; D014746:Vimentin; D000099259:N-myc Downstream-Regulated Gene 1 Protein
keywords: NDRG1; epithelial-mesenchymal transition; irinotecan; metastatic colorectal cancer