title: Expression of signal-induced proliferation-associated gene 1 (SIPA1), a RapGTPase-activating protein, is increased in colorectal cancer and has diverse effects on functions of colorectal cancer cells.
abstract: BACKGROUND
  Signal-induced proliferation-associated gene 1 (SIPA1) codes for a GTPase-activating protein, known to be a negative regulator of Ras-related Protein (RAP) which belongs to the Ras superfamily. It has been implicated in certain malignancies, including leukemia, cervical cancer and breast cancer. However the role of this molecule in colorectal cancer remains unknown. The current study aimed to investigate the expression of SIPA1 in colorectal tumour tissues and its impact on the function of colorectal cancer cells.
  
  
  METHODS
  A total of 94 colorectal cancer tissues together with 80 normal background tissues were used to examine the expression of SIPA1 transcript and protein using real-time quantitative Polymerase Chain Reaction (PCR) and immunohistochemical methods, respectively. Any association with clinical and histopathological characteristics was then identified. Ribozyme transgenes targeting SIPA1 were prepared to knockdown the expression of SIPA1 in colorectal cancer cells. The impact on their functions was subsequently determined, using respective in vitro function assays.
  
  
  RESULTS
  An increased expression of SIPA1 was evident in colorectal cancer tissues compared with its expression in normal background tissues (p<0.001). In colorectal tumours, its expression appeared to be lower in poorly-differentiated samples and in patients who had lymphatic metastasis. Knockdown of SIPA1 in colorectal cancer cells resulted in reduced cell growth in vitro. The knockdown exhibited a contrasting effect on invasion and migration, both of which were increased in SIPA1-knockdown cells compared with the controls.
  
  
  CONCLUSIONS
  SIPA1 is up-regulated in colorectal cancer. This suggests that SIPA1 plays diverse roles during disease progression as has contrasting effects on growth and motility of colorectal cancer cells.
authors.affiliation: Metastasis and Angiogenesis Research Group, Cardiff University School of Medicine, Heath Park, Cardiff, U.K. jiangw@cf.ac.uk
authors.forename: Ke
authors.initials: K
authors.lastname: Ji
authors.forename: Lin
authors.initials: L
authors.lastname: Ye
authors.forename: Anne-Marie
authors.initials: AM
authors.lastname: Toms
authors.forename: Rachel
authors.initials: R
authors.lastname: Hargest
authors.forename: Tracey A
authors.initials: TA
authors.lastname: Martin
authors.forename: Fiona
authors.initials: F
authors.lastname: Ruge
authors.forename: Jiafu
authors.initials: J
authors.lastname: Ji
authors.forename: Wen G
authors.initials: WG
authors.lastname: Jiang
mesh_terms: D018938:Caco-2 Cells; D016022:Case-Control Studies; D015179:Colorectal Neoplasms / Q000201:enzymology* / Q000235:genetics* / Q000473:pathology; D018450:Disease Progression; D020690:GTPase-Activating Proteins / Q000235:genetics / Q000378:metabolism*; D015972:Gene Expression Regulation, Neoplastic; D055785:Gene Knockdown Techniques; D006801:Humans; D007150:Immunohistochemistry; D053208:Kaplan-Meier Estimate; D008207:Lymphatic Metastasis / Q000473:pathology; D009363:Neoplasm Proteins / Q000235:genetics / Q000378:metabolism; D009360:Neoplastic Cells, Circulating / Q000378:metabolism / Q000473:pathology; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism*; D016337:RNA, Catalytic / Q000235:genetics / Q000378:metabolism; D060888:Real-Time Polymerase Chain Reaction / Q000379:methods; D019076:Transgenes; D015854:Up-Regulation
chemical_list: D020690:GTPase-Activating Proteins; D009363:Neoplasm Proteins; D009687:Nuclear Proteins; D016337:RNA, Catalytic; C490403:SIPA1 protein, human