title: Implication of metastasis suppressor gene, Kiss-1 and its receptor Kiss-1R in colorectal cancer.
abstract: BACKGROUND
  Kiss-1 and Kiss-1R have been suggested as a novel pair of metastasis suppressors for several human solid tumours, however, their role in colorectal cancer remains largely unknown. Therefore, the aim of this study was to investigate the role and signal transduction of Kiss-1 and Kiss-1R in colorectal cancer.
  
  
  METHODS
  Ribozyme transgenes were used to knockdown high expression of Kiss-1 and Kiss-1R in HT115 and HRT18 cells. The stabilized transfected cells were then used to deduce the influence of Kiss-1 and Kiss-1R on the function of colorectal cancer cells by in vitro assays and ECIS assay. The effect of Kiss-1 on MMPs related to tumour metastasis was also deleted by zymography. The mRNA and protein expression of Kiss-1 and Kiss-1R, and their correlation to the clinical outcome in human colorectal cancer were investigated using real-time PCR and IHC respectively.
  
  
  RESULTS
  Knocking down Kiss-1 resulted in increased invasion and migration of colorectal cancer cells. Kisspeptin-10 decreased cellular migration of colorectal cancer cells and required ERK signaling as shown during the ECIS based analyses. Reduction of MMP-9 was caused by Kisspeptin-10 and ERK inhibitor, shown by zymography. In human colorectal cancer tissues, the mRNA expression level of Kiss-1 had a negative correlation with Dukes staging, TNM staging, tumour size and lymph node involvement. Reduction of Kiss-1R was also linked to poor prognosis for the patients.
  
  
  CONCLUSIONS
  The present study has presented evidence that Kiss-1 may be a putative metastasis suppressor molecule in human colorectal cancer.
authors.forename: Ke
authors.initials: K
authors.lastname: Ji
authors.forename: Lin
authors.initials: L
authors.lastname: Ye
authors.forename: Fiona
authors.initials: F
authors.lastname: Ruge
authors.forename: Rachel
authors.initials: R
authors.lastname: Hargest
authors.forename: Malcolm D
authors.initials: MD
authors.lastname: Mason
authors.affiliation: Cardiff University-Peking University Joint Oncology Institute, Metastasis & Angiogenesis Research Group, Cardiff University School of Medicine, Cardiff CF14 4XN, UK. jiangw@cardiff.ac.uk.
authors.forename: Wen G
authors.initials: WG
authors.lastname: Jiang
mesh_terms: D000230:Adenocarcinoma / Q000378:metabolism* / Q000401:mortality / Q000556:secondary / Q000628:therapy; D045744:Cell Line, Tumor; D002465:Cell Movement; D059248:Chemoradiotherapy; D003106:Colon / Q000378:metabolism; D015179:Colorectal Neoplasms / Q000378:metabolism* / Q000401:mortality / Q000473:pathology / Q000628:therapy; D015870:Gene Expression; D006801:Humans; D053208:Kaplan-Meier Estimate; D059648:Kisspeptins / Q000235:genetics* / Q000378:metabolism; D020935:MAP Kinase Signaling System; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism; D015999:Multivariate Analysis; D011379:Prognosis; D043562:Receptors, G-Protein-Coupled / Q000235:genetics* / Q000378:metabolism; D000074502:Receptors, Kisspeptin-1; D016896:Treatment Outcome
chemical_list: C106628:KISS1 protein, human; C118688:KISS1R protein, human; D059648:Kisspeptins; D043562:Receptors, G-Protein-Coupled; D000074502:Receptors, Kisspeptin-1; C579270:MMP9 protein, human; D020780:Matrix Metalloproteinase 9