title: PBX3 promotes migration and invasion of colorectal cancer cells via activation of MAPK/ERK signaling pathway.
abstract: OBJECTIVE
  To investigate the role of pre-B-cell leukemia homeobox (PBX)3 in migration and invasion of colorectal cancer (CRC) cells.
  
  
  METHODS
  We detected PBX3 expression in five cell lines and surgical specimens from 111 patients with CRC using real-time reverse transcription-polymerase chain reaction. We forced expression of PBX3 in low metastatic HT-29 and SW480 cells and knocked down expression of PBX3 in highly metastatic LOVO and HCT-8 cells. Wound healing and Boyden chamber assays were used to detect cell migration and invasion after altered expression of PBX3. Western blot was performed to detect the change of signaling molecule ERK1/2 following PBX3 overexpression.
  
  
  RESULTS
  High level of PBX3 expression was correlated with the invasive potential of CRC cells, and significantly associated with lymph node invasion (P = 0.02), distant metastasis (P = 0.04), advanced TNM stage (P = 0.03) and poor overall survival of patients (P < 0.05). Ectopic expression of PBX3 in low metastatic cells was shown to promote migration and invasion, while inhibited PBX3 expression in highly metastatic cells suppressed migration and invasion. Furthermore, upregulation of phosphorylated extracellular signal-regulated kinase (ERK)1/2 was found to be one of the targeted molecules responsible for PBX3-induced CRC cell migration and invasion.
  
  
  CONCLUSIONS
  PBX3 induces invasion and metastasis of CRC cells partially through activation of the MAPK/ERK signaling pathway.
authors.affiliation: Hai-Bo Han, Yuan Zhang, Wei Zhao, Li-Min Wang, Zhi-Qian Zhang, Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Department of Cell Biology, Peking University Cancer Hospital and Institute, Beijing 100142, China.
authors.forename: Hai-Bo
authors.initials: HB
authors.lastname: Han
authors.affiliation: Hai-Bo Han, Yuan Zhang, Wei Zhao, Li-Min Wang, Zhi-Qian Zhang, Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Department of Cell Biology, Peking University Cancer Hospital and Institute, Beijing 100142, China.
authors.forename: Jin
authors.initials: J
authors.lastname: Gu
authors.affiliation: Hai-Bo Han, Yuan Zhang, Wei Zhao, Li-Min Wang, Zhi-Qian Zhang, Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Department of Cell Biology, Peking University Cancer Hospital and Institute, Beijing 100142, China.
authors.forename: Deng-Bo
authors.initials: DB
authors.lastname: Ji
authors.affiliation: Hai-Bo Han, Yuan Zhang, Wei Zhao, Li-Min Wang, Zhi-Qian Zhang, Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Department of Cell Biology, Peking University Cancer Hospital and Institute, Beijing 100142, China.
authors.forename: Zhao-Wei
authors.initials: ZW
authors.lastname: Li
authors.affiliation: Hai-Bo Han, Yuan Zhang, Wei Zhao, Li-Min Wang, Zhi-Qian Zhang, Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Department of Cell Biology, Peking University Cancer Hospital and Institute, Beijing 100142, China.
authors.forename: Yuan
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Hai-Bo Han, Yuan Zhang, Wei Zhao, Li-Min Wang, Zhi-Qian Zhang, Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Department of Cell Biology, Peking University Cancer Hospital and Institute, Beijing 100142, China.
authors.forename: Wei
authors.initials: W
authors.lastname: Zhao
authors.affiliation: Hai-Bo Han, Yuan Zhang, Wei Zhao, Li-Min Wang, Zhi-Qian Zhang, Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Department of Cell Biology, Peking University Cancer Hospital and Institute, Beijing 100142, China.
authors.forename: Li-Min
authors.initials: LM
authors.lastname: Wang
authors.affiliation: Hai-Bo Han, Yuan Zhang, Wei Zhao, Li-Min Wang, Zhi-Qian Zhang, Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Department of Cell Biology, Peking University Cancer Hospital and Institute, Beijing 100142, China.
authors.forename: Zhi-Qian
authors.initials: ZQ
authors.lastname: Zhang
mesh_terms: D002465:Cell Movement / Q000187:drug effects; D015179:Colorectal Neoplasms / Q000201:enzymology* / Q000235:genetics / Q000401:mortality / Q000473:pathology; D004789:Enzyme Activation; D005260:Female; D019073:HT29 Cells; D018398:Homeodomain Proteins / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D053208:Kaplan-Meier Estimate; D008207:Lymphatic Metastasis; D020935:MAP Kinase Signaling System / Q000187:drug effects; D008297:Male; D008875:Middle Aged; D019950:Mitogen-Activated Protein Kinase 1 / Q000037:antagonists & inhibitors / Q000378:metabolism*; D048052:Mitogen-Activated Protein Kinase 3 / Q000037:antagonists & inhibitors / Q000378:metabolism*; D009361:Neoplasm Invasiveness; D009367:Neoplasm Staging; D010766:Phosphorylation; D047428:Protein Kinase Inhibitors / Q000494:pharmacology; D011518:Proto-Oncogene Proteins / Q000235:genetics / Q000378:metabolism*; D034622:RNA Interference; D013997:Time Factors; D014162:Transfection
chemical_list: D018398:Homeodomain Proteins; D047428:Protein Kinase Inhibitors; D011518:Proto-Oncogene Proteins; C090466:proto-oncogene protein Pbx3; C535150:MAPK1 protein, human; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3
keywords: Cell invasion; Cell migration; Colorectal cancer; Mitogen-activated protein kinase signaling pathway; Pre-B-cell leukemia homeobox 3