title: The SIX1-EYA transcriptional complex as a therapeutic target in cancer.
abstract: BACKGROUND
  The SIX homeodomain proteins and the eyes absent (EYA) family of co-activators form a bipartite transcription factor complex that promotes the proliferation and survival of progenitor cells during organogenesis and is down-regulated in most adult tissues. Abnormal over-expression of SIX1 and EYA in adult tissue is associated with the initiation and progression of diverse tumor types. Importantly, SIX1 and EYA are often co-overexpressed in tumors, and the SIX1-EYA2 interaction has been shown to be critical for metastasis in a breast cancer model. The EYA proteins also contain protein tyrosine phosphatase activity, which plays an important role in breast cancer growth and metastasis as well as directing cells to the repair pathway upon DNA damage.
  
  
  METHODS
  This review provides a summary of the SIX1/EYA complex as it relates to development and disease and the current efforts to therapeutically target this complex.
  
  
  CONCLUSIONS
  Recently, there have been an increasing number of studies suggesting that targeting the SIX1/EYA transcriptional complex will potently inhibit tumor progression. Although current attempts to develop inhibitors targeting this complex are still in the early stages, continued efforts toward developing better compounds may ultimately result in effective anti-cancer therapies.
authors.affiliation: University of Colorado Anschutz Medical Campus, Department of Biochemistry and Molecular Genetics , Aurora, CO 80045 , USA Heide.Ford@UCDenver.edu , Rui.zhao@ucdenver.edu.
authors.forename: Melanie A
authors.initials: MA
authors.lastname: Blevins
authors.forename: Christina G
authors.initials: CG
authors.lastname: Towers
authors.forename: Aaron N
authors.initials: AN
authors.lastname: Patrick
authors.forename: Rui
authors.initials: R
authors.lastname: Zhao
authors.forename: Heide L
authors.initials: HL
authors.lastname: Ford
mesh_terms: D000328:Adult; D000818:Animals; D001943:Breast Neoplasms / Q000188:drug therapy / Q000235:genetics / Q000473:pathology; D018450:Disease Progression; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D018398:Homeodomain Proteins / Q000235:genetics*; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics*; D058990:Molecular Targeted Therapy; D009362:Neoplasm Metastasis / Q000235:genetics; D009369:Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology; D009687:Nuclear Proteins / Q000235:genetics*; D017027:Protein Tyrosine Phosphatases / Q000235:genetics*
chemical_list: D018398:Homeodomain Proteins; D047908:Intracellular Signaling Peptides and Proteins; D009687:Nuclear Proteins; C099236:SIX1 protein, human; C106938:EYA2 protein, human; D017027:Protein Tyrosine Phosphatases
keywords: inhibition of transcriptional complexes; metastasis; phosphatase; protein–protein interaction; six1/eyes absent complex; transcription factor