title: TPX2 is a novel prognostic marker for the growth and metastasis of colon cancer.
abstract: BACKGROUND
  We have previously demonstrated an aberrant overexpression of the microtubule-associated protein TPX2 in colon cancer using a genome-wide gene expression profiling analysis. Here, we aim to investigate its expression pattern, clinical significance, and biological function in colon cancer.
  
  
  METHODS
  TPX2 expression was analyzed in human colon cancer cell lines and tumor samples. The effect of TPX2 on cell proliferation, tumorigenesis, and metastasis was examined in vitro and in vivo.
  
  
  RESULTS
  TPX2 was overexpressed in 129 of the 203 (60.8%) colon cancer metastatic lesions, with the expression being significantly higher than that in primary cancerous tissue and normal colon mucosa. Overexpression of TPX2 was significantly associated with clinical staging, vessel invasion, and metastasis. In survival analyses, patients with TPX2 overexpression had worse overall survival and metastasis free survival, suggesting that deregulation of TPX2 may contribute to the metastasis of colon cancer. Consistent with this, suppression of TPX2 expression inhibited proliferation and tumorigenicity of colon cancer cells both in vitro and in vivo. Strikingly, we found that TPX2 knockdown significantly attenuated the migration and invasion ability of colon cancer cells, which was further shown to be mechanistically associated with AKT-mediated MMP2 activity.
  
  
  CONCLUSIONS
  These findings suggest that TPX2 plays an important role in promoting tumorigenesis and metastasis of human colon cancer, and may represent a novel prognostic biomarker and therapeutic target for the disease.
authors.forename: Ping
authors.initials: P
authors.lastname: Wei
authors.forename: Nu
authors.initials: N
authors.lastname: Zhang
authors.forename: Ye
authors.initials: Y
authors.lastname: Xu
authors.forename: Xinxiang
authors.initials: X
authors.lastname: Li
authors.forename: Debing
authors.initials: D
authors.lastname: Shi
authors.forename: Yuwei
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Department of Colorectal Surgery, Fudan University Shanghai Cancer Center, Shanghai 200032, China. davidleehero@126.com.
authors.forename: Dawei
authors.initials: D
authors.lastname: Li
authors.forename: Sanjun
authors.initials: S
authors.lastname: Cai
mesh_terms: D000368:Aged; D000818:Animals; D001483:Base Sequence; D014408:Biomarkers, Tumor / Q000235:genetics / Q000378:metabolism*; D018797:Cell Cycle Proteins / Q000235:genetics / Q000378:metabolism*; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D003110:Colonic Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D017931:DNA Primers; D005260:Female; D020868:Gene Silencing; D064593:Heterografts; D006801:Humans; D008207:Lymphatic Metastasis; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008869:Microtubule-Associated Proteins / Q000235:genetics / Q000378:metabolism*; D008875:Middle Aged; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism*; D011379:Prognosis; D060888:Real-Time Polymerase Chain Reaction
chemical_list: D014408:Biomarkers, Tumor; D018797:Cell Cycle Proteins; D017931:DNA Primers; D008869:Microtubule-Associated Proteins; D009687:Nuclear Proteins; C122167:TPX2 protein, human