title: Elevated HOXB9 expression promotes differentiation and predicts a favourable outcome in colon adenocarcinoma patients.
abstract: BACKGROUND
  Little is known about the tumour suppressive proteins and the underlying mechanisms that suppress colon cancer progression. Homeodomain-containing transcription factor HOXB9 plays an important role in embryogenesis and cancer development. We here aim to uncover the potential role of HOXB9 in the regulation of colon adenocarcinoma progression including epithelial-to-mesenchymal transition.
  
  
  METHODS
  HOXB9 expression in colon adenocarcinoma cells and patients was analysed by western blot and immunohistochemistry separately. Correlation between HOXB9 expressions with patients' survival was assessed by Kaplan-Meier analysis. HOXB9-regulated target gene expression was determined by RNA sequencing in HOXB9-overexpressing colon adenocarcinoma cells.
  
  
  RESULTS
  Elevated HOXB9 expression was identified in well-differentiated colon adenocarcinoma patients and was associated with a better overall patients' survival. Overexpression of HOXB9 inhibited colon adenocarcinoma cell growth, migration, invasion in vitro and tumour growth, liver as well as lung metastases in nude mice; whereas silencing HOXB9 promoted these functions. HOXB9 promoted colon adenocarcinoma differentiation via a mechanism that stimulates mesenchymal-to-epithelial transition, involving downregulation of EMT-promoting transcriptional factors including Snail, Twist, FOXC2 and ZEB1 and upregulation of epithelial proteins including E-cadherin, claudins-1, -4, -7, occludin and ZO-1.
  
  
  CONCLUSIONS
  HOXB9 is a novel tumour suppressor that inhibits colon adenocarcinoma progression by inducing differentiation. Elevated expression of HOXB9 predicts a longer survival in colon adenocarcinoma patients.
authors.affiliation: 1] Key Laboratory of Carcinogenesis and Translational Research, Ministry of Education, Peking University Health Science Center, Beijing 100191, China [2] State Key Laboratory of Natural and Biomimetic Drugs, Peking University Health Science Center, Beijing 100191, China [3] Laboratory of Molecular Cell Biology and Tumor Biology, Department of Anatomy, Histology and Embryology, Peking University Health Science Center, Beijing 100191, China.
authors.forename: J
authors.initials: J
authors.lastname: Zhan
authors.affiliation: 1] Key Laboratory of Carcinogenesis and Translational Research, Ministry of Education, Peking University Health Science Center, Beijing 100191, China [2] State Key Laboratory of Natural and Biomimetic Drugs, Peking University Health Science Center, Beijing 100191, China [3] Laboratory of Molecular Cell Biology and Tumor Biology, Department of Anatomy, Histology and Embryology, Peking University Health Science Center, Beijing 100191, China.
authors.forename: M
authors.initials: M
authors.lastname: Niu
authors.affiliation: 1] Key Laboratory of Carcinogenesis and Translational Research, Ministry of Education, Peking University Health Science Center, Beijing 100191, China [2] State Key Laboratory of Natural and Biomimetic Drugs, Peking University Health Science Center, Beijing 100191, China [3] Laboratory of Molecular Cell Biology and Tumor Biology, Department of Anatomy, Histology and Embryology, Peking University Health Science Center, Beijing 100191, China.
authors.forename: P
authors.initials: P
authors.lastname: Wang
authors.affiliation: 1] Key Laboratory of Carcinogenesis and Translational Research, Ministry of Education, Peking University Health Science Center, Beijing 100191, China [2] Laboratory of Molecular Pathology, Department of Pathology, Peking University Health Science Center, Beijing 100191, China.
authors.forename: X
authors.initials: X
authors.lastname: Zhu
authors.affiliation: 1] Key Laboratory of Carcinogenesis and Translational Research, Ministry of Education, Peking University Health Science Center, Beijing 100191, China [2] State Key Laboratory of Natural and Biomimetic Drugs, Peking University Health Science Center, Beijing 100191, China [3] Laboratory of Molecular Cell Biology and Tumor Biology, Department of Anatomy, Histology and Embryology, Peking University Health Science Center, Beijing 100191, China.
authors.forename: S
authors.initials: S
authors.lastname: Li
authors.affiliation: 1] Key Laboratory of Carcinogenesis and Translational Research, Ministry of Education, Peking University Health Science Center, Beijing 100191, China [2] State Key Laboratory of Natural and Biomimetic Drugs, Peking University Health Science Center, Beijing 100191, China [3] Laboratory of Molecular Cell Biology and Tumor Biology, Department of Anatomy, Histology and Embryology, Peking University Health Science Center, Beijing 100191, China.
authors.forename: J
authors.initials: J
authors.lastname: Song
authors.affiliation: 1] Key Laboratory of Carcinogenesis and Translational Research, Ministry of Education, Peking University Health Science Center, Beijing 100191, China [2] Laboratory of Molecular Pathology, Department of Pathology, Peking University Health Science Center, Beijing 100191, China.
authors.forename: H
authors.initials: H
authors.lastname: He
authors.affiliation: 1] Key Laboratory of Carcinogenesis and Translational Research, Ministry of Education, Peking University Health Science Center, Beijing 100191, China [2] State Key Laboratory of Natural and Biomimetic Drugs, Peking University Health Science Center, Beijing 100191, China [3] Institute of Cardiovascular Research, Peking University Health Science Center, Beijing 100191, China.
authors.forename: Y
authors.initials: Y
authors.lastname: Wang
authors.affiliation: 1] Key Laboratory of Carcinogenesis and Translational Research, Ministry of Education, Peking University Health Science Center, Beijing 100191, China [2] Department of Biochemistry, Peking University Health Science Center, Beijing 100191, China.
authors.forename: L
authors.initials: L
authors.lastname: Xue
authors.affiliation: 1] Key Laboratory of Carcinogenesis and Translational Research, Ministry of Education, Peking University Health Science Center, Beijing 100191, China [2] Laboratory of Molecular Pathology, Department of Pathology, Peking University Health Science Center, Beijing 100191, China.
authors.forename: W
authors.initials: W
authors.lastname: Fang
authors.affiliation: 1] Key Laboratory of Carcinogenesis and Translational Research, Ministry of Education, Peking University Health Science Center, Beijing 100191, China [2] State Key Laboratory of Natural and Biomimetic Drugs, Peking University Health Science Center, Beijing 100191, China [3] Laboratory of Molecular Cell Biology and Tumor Biology, Department of Anatomy, Histology and Embryology, Peking University Health Science Center, Beijing 100191, China.
authors.forename: H
authors.initials: H
authors.lastname: Zhang
mesh_terms: D000230:Adenocarcinoma / Q000235:genetics* / Q000473:pathology*; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000818:Animals; D002454:Cell Differentiation / Q000235:genetics*; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000235:genetics; D049109:Cell Proliferation; D003110:Colonic Neoplasms / Q000235:genetics* / Q000473:pathology*; D018450:Disease Progression; D015536:Down-Regulation / Q000235:genetics; D058750:Epithelial-Mesenchymal Transition / Q000235:genetics; D005260:Female; D015972:Gene Expression Regulation, Neoplastic / Q000235:genetics; D045325:HCT116 Cells; D018398:Homeodomain Proteins / Q000235:genetics*; D006801:Humans; D008113:Liver Neoplasms / Q000473:pathology / Q000556:secondary; D008175:Lung Neoplasms / Q000473:pathology / Q000556:secondary; D008297:Male; D051379:Mice; D008819:Mice, Nude; D008875:Middle Aged; D014157:Transcription Factors / Q000235:genetics; D015854:Up-Regulation / Q000235:genetics; D055815:Young Adult
chemical_list: C491257:HOXB9 protein, human; D018398:Homeodomain Proteins; D014157:Transcription Factors