The SIX1-EYA transcriptional complex as a therapeutic target in cancer
- 11 December 2014
- journal article
- review article
- Published by Taylor & Francis Ltd in Emerging Therapeutic Targets
- Vol. 19 (2), 213-225
- https://doi.org/10.1517/14728222.2014.978860
Abstract
Introduction: 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. Areas covered: 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. Expert opinion: 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.Keywords
This publication has 110 references indexed in Scilit:
- Effect of the MDM2 antagonist RG7112 on the P53 pathway in patients with MDM2-amplified, well-differentiated or dedifferentiated liposarcoma: an exploratory proof-of-mechanism studyThe Lancet Oncology, 2012
- Epigenetic repression of cardiac progenitor gene expression by Ezh2 is required for postnatal cardiac homeostasisNature Genetics, 2012
- Definition and classification of cancer cachexia: an international consensusThe Lancet Oncology, 2011
- Six1 transcription factor is critical for coordination of epithelial, mesenchymal and vascular morphogenesis in the mammalian lungDevelopmental Biology, 2011
- Hallmarks of Cancer: The Next GenerationCell, 2011
- Tyrosine dephosphorylation of H2AX modulates apoptosis and survival decisionsNature, 2009
- The sine oculis homeobox (SIX) family of transcription factors as regulators of development and diseaseCellular and Molecular Life Sciences, 2008
- Branchio-oto-renal syndrome (BOR): novel mutations in theEYA1gene, and a review of the mutational genetics of BORHuman Mutation, 2008
- Eya protein phosphatase activity regulates Six1–Dach–Eya transcriptional effects in mammalian organogenesisNature, 2003
- A human homologue of the Drosophila eyes absent gene underlies Branchio-Oto-Renal (BOR) syndrome and identifies a novel gene familyNature Genetics, 1997