title: The roles of HOXD10 in the development and progression of head and neck squamous cell carcinoma (HNSCC).
abstract: BACKGROUND
  HOX gene expression is altered in many cancers; previous microarray revealed changes in HOX gene expression in head and neck squamous cell carcinoma (HNSCC), particularly HOXD10.
  
  
  METHODS
  HOXD10 expression was assessed by qPCR and immunoblotting in vitro and by immunohistochemistry (IHC) in tissues. Low-expressing cells were stably transfected with HOXD10 and the phenotype assessed with MTS, migration and adhesion assays and compared with the effects of siRNA knockdown in high-HOXD10-expressing cells. Novel HOXD10 targets were identified using expression microarrays, confirmed by reporter assay, and validated in tissues using IHC.
  
  
  RESULTS
  HOXD10 expression was low in NOKs, high in most primary tumour cells, and low in lymph node metastasis cells, a pattern confirmed using IHC in tissues. Overexpression of HOXD10 decreased cell invasion but increased proliferation, adhesion and migration, with knockdown causing reciprocal effects. There was no consistent effect on apoptosis. Microarray analysis identified several putative HOXD10-responsive genes, including angiomotin (AMOT-p80) and miR-146a. These were confirmed as HOXD10 targets by reporter assay. Manipulation of AMOT-p80 expression resulted in phenotypic changes similar to those on manipulation of HOXD10 expression.
  
  
  CONCLUSIONS
  HOXD10 expression varies by stage of disease and produces differential effects: high expression giving cancer cells a proliferative and migratory advantage, and low expression may support invasion/metastasis, in part, by modulating AMOT-p80 levels.
authors.affiliation: 1] Unit of Oral & Maxillofacial Pathology, School of Clinical Dentistry, University of Sheffield, Sheffield S10 2TA, UK [2] Department of Pathology and Laboratory Medicine, King Abdulaziz Medical City-WR, Jeddah, Saudi Arabia.
authors.forename: F
authors.initials: F
authors.lastname: Hakami
authors.affiliation: Unit of Oral & Maxillofacial Pathology, School of Clinical Dentistry, University of Sheffield, Sheffield S10 2TA, UK.
authors.forename: L
authors.initials: L
authors.lastname: Darda
authors.affiliation: Unit of Oral & Maxillofacial Pathology, School of Clinical Dentistry, University of Sheffield, Sheffield S10 2TA, UK.
authors.forename: P
authors.initials: P
authors.lastname: Stafford
authors.affiliation: Academic Unit of Clinical Oncology, University of Sheffield, Sheffield S10 2SJ, UK.
authors.forename: P
authors.initials: P
authors.lastname: Woll
authors.affiliation: Unit of Oral & Maxillofacial Pathology, School of Clinical Dentistry, University of Sheffield, Sheffield S10 2TA, UK.
authors.forename: D W
authors.initials: DW
authors.lastname: Lambert
authors.affiliation: 1] Unit of Oral & Maxillofacial Pathology, School of Clinical Dentistry, University of Sheffield, Sheffield S10 2TA, UK [2] Department of Oral Pathology and Biology, University of Pretoria, Pretoria, South Africa.
authors.forename: K D
authors.initials: KD
authors.lastname: Hunter
mesh_terms: D000091082:Angiomotins; D002294:Carcinoma, Squamous Cell / Q000378:metabolism* / Q000473:pathology; D045744:Cell Line, Tumor; D018450:Disease Progression; D015972:Gene Expression Regulation, Neoplastic; D006258:Head and Neck Neoplasms / Q000378:metabolism* / Q000473:pathology; D018398:Homeodomain Proteins / Q000502:physiology*; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins / Q000235:genetics; D008565:Membrane Proteins / Q000235:genetics; D035683:MicroRNAs / Q000235:genetics; D008840:Microfilament Proteins; D020411:Oligonucleotide Array Sequence Analysis; D011401:Promoter Regions, Genetic; D000077195:Squamous Cell Carcinoma of Head and Neck; D014157:Transcription Factors / Q000502:physiology*; D059467:Transcriptome
chemical_list: C423985:AMOT protein, human; D000091082:Angiomotins; D018398:Homeodomain Proteins; D036341:Intercellular Signaling Peptides and Proteins; C542542:MIRN146 microRNA, human; D008565:Membrane Proteins; D035683:MicroRNAs; D008840:Microfilament Proteins; D014157:Transcription Factors; C072064:HOXD10 protein, human