SIX1

Summary

Gene Symbol: SIX1
Description: SIX homeobox 1
Alias: BOS3, DFNA23, TIP39, homeobox protein SIX1, sine oculis homeobox homolog 1
Species: human
Products:     SIX1

Top Publications

  1. Tan J, Zhang C, QIAN J. Expression and significance of Six1 and Ezrin in cervical cancer tissue. Tumour Biol. 2011;32:1241-7 pubmed publisher
    This study aimed to investigate the expression of Six1 gene and its downstream target gene Ezrin in cervical cancer, and to correlate their expression to the clinical pathology of cervical cancer...
  2. Zheng X, Liang P, Guo J, Zheng Y, Han J, Yu L, et al. Expression and clinical implications of homeobox gene Six1 in cervical cancer cell lines and cervical epithelial tissues. Int J Gynecol Cancer. 2010;20:1587-92 pubmed
    The homeobox gene Six1 is overexpressed in multiple human tumors, playing a role in promoting tumorigenesis and metastasis. The present study was aimed to investigate the clinical implications of Six1 expression in cervical cancer...
  3. Buller C, Xu X, Marquis V, Schwanke R, Xu P. Molecular effects of Eya1 domain mutations causing organ defects in BOR syndrome. Hum Mol Genet. 2001;10:2775-81 pubmed
    ..However, four mutations are crucial for protein-protein interactions in both yeast and mammalian cells. Our results provide insights into the molecular mechanisms of organ defects detected in human syndromes. ..
  4. Ng K, Lee T, Cheng Q, Wo J, Sun C, Guo D, et al. Suppression of tumorigenesis and metastasis of hepatocellular carcinoma by shRNA interference targeting on homeoprotein Six1. Int J Cancer. 2010;127:859-72 pubmed publisher
    We previously demonstrated that the overexpression of homeoprotein Six1 in hepatocellular carcinoma (HCC) patients is associated with venous infiltration, advanced pathologic tumor metastasis (pTNM) stage and poor overall survival rate (..
  5. Micalizzi D, Christensen K, Jedlicka P, Coletta R, Baron A, Harrell J, et al. The Six1 homeoprotein induces human mammary carcinoma cells to undergo epithelial-mesenchymal transition and metastasis in mice through increasing TGF-beta signaling. J Clin Invest. 2009;119:2678-90 pubmed publisher
    ..Here we show that overexpression of the homeoprotein Six1, normally a developmentally restricted transcriptional regulator, increases TGF-beta signaling in human breast ..
  6. McCoy E, Iwanaga R, Jedlicka P, Abbey N, Chodosh L, Heichman K, et al. Six1 expands the mouse mammary epithelial stem/progenitor cell pool and induces mammary tumors that undergo epithelial-mesenchymal transition. J Clin Invest. 2009;119:2663-77 pubmed publisher
    b>Six1 is a developmentally regulated homeoprotein with limited expression in most normal adult tissues and frequent misexpression in a variety of malignancies...
  7. Oliver G, Wehr R, Jenkins N, Copeland N, Cheyette B, Hartenstein V, et al. Homeobox genes and connective tissue patterning. Development. 1995;121:693-705 pubmed
    ..Six 1 and Six 2 also are expressed in skeletal and smooth muscle, respectively. These genes may participate in the patterning of the distal tendons of the limb phalanges by setting positional values along the limb axes. ..
  8. Jin A, Xu Y, Liu S, Jin T, Li Z, Jin H, et al. Sineoculis homeobox homolog 1 protein overexpression as an independent biomarker for pancreatic ductal adenocarcinoma. Exp Mol Pathol. 2014;96:54-60 pubmed publisher
    Sineoculis homeobox homolog 1 (SIX1) is a member of the SIX gene family. It is highly expressed in cancers derived from tissues that play a fundamental role during embryogenesis...
  9. Ono H, Imoto I, Kozaki K, Tsuda H, Matsui T, Kurasawa Y, et al. SIX1 promotes epithelial-mesenchymal transition in colorectal cancer through ZEB1 activation. Oncogene. 2012;31:4923-34 pubmed publisher
    ..analysis using epithelial- and mesenchymal-like CRC cell lines, and following the ontology (GO) analysis, SIX1 gene was identified to be an EMT-related gene in CRC...

More Information

Publications84

  1. Krug P, Moriniere V, Marlin S, Koubi V, Gabriel H, Colin E, et al. Mutation screening of the EYA1, SIX1, and SIX5 genes in a large cohort of patients harboring branchio-oto-renal syndrome calls into question the pathogenic role of SIX5 mutations. Hum Mutat. 2011;32:183-90 pubmed publisher
    ..Over 80 mutations in EYA1 have been reported in BOR. Mutations in SIX1, a DNA binding protein that associates with EYA1, have been reported less frequently...
  2. Ramdas W, van Koolwijk L, Ikram M, Jansonius N, De Jong P, Bergen A, et al. A genome-wide association study of optic disc parameters. PLoS Genet. 2010;6:e1000978 pubmed publisher
    ..15x10(-11)) in the CDKN2B gene and rs10483727 on chromosome 14q22.3-q23 (p = 2.93x10(-10)) within 40 kbp of the SIX1 gene...
  3. Macgregor S, Hewitt A, Hysi P, Ruddle J, Medland S, Henders A, et al. Genome-wide association identifies ATOH7 as a major gene determining human optic disc size. Hum Mol Genet. 2010;19:2716-24 pubmed publisher
    ..0136). Furthermore, the Arg65Gly variant was found to have very low frequency (0.00066) in an additional set of 672 controls. ..
  4. Patrick A, Schiemann B, Yang K, Zhao R, Ford H. Biochemical and functional characterization of six SIX1 Branchio-oto-renal syndrome mutations. J Biol Chem. 2009;284:20781-90 pubmed publisher
    ..Recently, eight mutations in the SIX1 homeobox gene were discovered in BOR patients...
  5. Coletta R, Christensen K, Micalizzi D, Jedlicka P, Varella Garcia M, Ford H. Six1 overexpression in mammary cells induces genomic instability and is sufficient for malignant transformation. Cancer Res. 2008;68:2204-13 pubmed publisher
    ..During embryogenesis, the Six1 homeoprotein is essential for the expansion of precursor cell populations that give rise to muscle and kidney, ..
  6. Ruf R, Xu P, Silvius D, Otto E, Beekmann F, Muerb U, et al. SIX1 mutations cause branchio-oto-renal syndrome by disruption of EYA1-SIX1-DNA complexes. Proc Natl Acad Sci U S A. 2004;101:8090-5 pubmed
    ..We recently mapped a locus for BOR/BO syndrome (BOS3) to human chromosome 14q23.1...
  7. Ford H, Kabingu E, Bump E, Mutter G, Pardee A. Abrogation of the G2 cell cycle checkpoint associated with overexpression of HSIX1: a possible mechanism of breast carcinogenesis. Proc Natl Acad Sci U S A. 1998;95:12608-13 pubmed
    ..These data support the role for homeobox genes in tumorigenesis/tumor progression, possibly through a cell cycle function. ..
  8. Ford H, Landesman Bollag E, Dacwag C, Stukenberg P, Pardee A, Seldin D. Cell cycle-regulated phosphorylation of the human SIX1 homeodomain protein. J Biol Chem. 2000;275:22245-54 pubmed
    Human SIX1 (HSIX1) is a member of the Six class of homeodomain proteins implicated in muscle, eye, head, and brain development...
  9. Ng K, Man K, Sun C, Lee T, Poon R, Lo C, et al. Clinicopathological significance of homeoprotein Six1 in hepatocellular carcinoma. Br J Cancer. 2006;95:1050-5 pubmed
    ..The present study investigated the clinicopathological significance of a possible metastasis regulator Six1 in HCC patients who were undergone hepatectomy...
  10. Kochhar A, Orten D, Sorensen J, Fischer S, Cremers C, Kimberling W, et al. SIX1 mutation screening in 247 branchio-oto-renal syndrome families: a recurrent missense mutation associated with BOR. Hum Mutat. 2008;29:565 pubmed publisher
    ..Both EYA1 and SIX1 are expressed in developing otic, branchial and renal tissue...
  11. Ramdas W, van Koolwijk L, Lemij H, Pasutto F, Cree A, Thorleifsson G, et al. Common genetic variants associated with open-angle glaucoma. Hum Mol Genet. 2011;20:2464-71 pubmed publisher
    ..The loci studied include ATOH7, CDC7/TGFBR3 and SALL1 for optic disc area, and CDKN2B, SIX1, SCYL1/LTBP3, CHEK2, ATOH7 and DCLK1 for VCDR...
  12. Zhang Y, Knosp B, Maconochie M, Friedman R, Smith R. A comparative study of Eya1 and Eya4 protein function and its implication in branchio-oto-renal syndrome and DFNA10. J Assoc Res Otolaryngol. 2004;5:295-304 pubmed
    ..We verified that bait constructs of the homologous region ( Eya1HR and Eya4HR) interact with Six1 prey constructs, although no interaction with Dach1 prey was demonstrable...
  13. Zheng W, Huang L, Wei Z, Silvius D, Tang B, Xu P. The role of Six1 in mammalian auditory system development. Development. 2003;130:3989-4000 pubmed
    ..However, their roles during auditory system development have not been studied. We report that Six1 is required for mouse auditory system development...
  14. Ikeda K, Watanabe Y, Ohto H, Kawakami K. Molecular interaction and synergistic activation of a promoter by Six, Eya, and Dach proteins mediated through CREB binding protein. Mol Cell Biol. 2002;22:6759-66 pubmed
    ..This work provides fundamental information on the role and the mechanism of action of this gene cassette in tissue differentiation and organogenesis. ..
  15. Fan X, Brass L, Poncz M, Spitz F, Maire P, Manning D. The alpha subunits of Gz and Gi interact with the eyes absent transcription cofactor Eya2, preventing its interaction with the six class of homeodomain-containing proteins. J Biol Chem. 2000;275:32129-34 pubmed
    ..We show here a novel functional regulation of a co-activator directly by G protein subunits. ..
  16. Springelkamp H, Höhn R, Mishra A, Hysi P, Khor C, Loomis S, et al. Meta-analysis of genome-wide association studies identifies novel loci that influence cupping and the glaucomatous process. Nat Commun. 2014;5:4883 pubmed publisher
    ..This study has more than doubled the known loci associated with optic disc cupping and will allow greater understanding of mechanisms involved in this common blinding condition. ..
  17. Wang C, Jedlicka P, Patrick A, Micalizzi D, Lemmer K, Deitsch E, et al. SIX1 induces lymphangiogenesis and metastasis via upregulation of VEGF-C in mouse models of breast cancer. J Clin Invest. 2012;122:1895-906 pubmed publisher
    ..We therefore investigated whether SIX1, a homeodomain-containing transcription factor previously associated in breast cancer with lymph node positivity, ..
  18. Osman W, Low S, Takahashi A, Kubo M, Nakamura Y. A genome-wide association study in the Japanese population confirms 9p21 and 14q23 as susceptibility loci for primary open angle glaucoma. Hum Mol Genet. 2012;21:2836-42 pubmed publisher
    ..Our GWAS results should contribute to better insight into the genetic basis of POAG. ..
  19. Li C, Guo M, Borczuk A, Powell C, Wei M, Thaker H, et al. Gene expression in Wilms' tumor mimics the earliest committed stage in the metanephric mesenchymal-epithelial transition. Am J Pathol. 2002;160:2181-90 pubmed
    ..are essential for cell survival and proliferation in early metanephric development, whereas others, including SIX1, MOX1, and SALL2, are predicted to act at this stage...
  20. Imam J, Buddavarapu K, Lee Chang J, Ganapathy S, Camosy C, Chen Y, et al. MicroRNA-185 suppresses tumor growth and progression by targeting the Six1 oncogene in human cancers. Oncogene. 2010;29:4971-9 pubmed publisher
    ..In this study, we investigate the mechanism by which the Six1 homeobox protein, which has a crucial role during development, is frequently deregulated in several poor outcome, ..
  21. Chai L, Yang J, Di C, Cui W, Kawakami K, Lai R, et al. Transcriptional activation of the SALL1 by the human SIX1 homeodomain during kidney development. J Biol Chem. 2006;281:18918-26 pubmed
    ..Consensus binding sites were identified for several transcription factors, with multiple sites for WT1 and SIX1. In transient transfection assays, SALL1 promoter activity was higher in HEK-293 human kidney cells and COS-7 ..
  22. Miller S, Lan Z, Hardiman A, Wu J, Kordich J, Patmore D, et al. Inhibition of Eyes Absent Homolog 4 expression induces malignant peripheral nerve sheath tumor necrosis. Oncogene. 2010;29:368-79 pubmed publisher
    ..We identified a decrease in DACH1 expression, and increases in the expressions of PAX6, EYA1, EYA2, EYA4, and SIX1-4 genes...
  23. Li X, Oghi K, Zhang J, Krones A, Bush K, Glass C, et al. Eya protein phosphatase activity regulates Six1-Dach-Eya transcriptional effects in mammalian organogenesis. Nature. 2003;426:247-54 pubmed
    ..Here, we report that Six1 is required for the development of murine kidney, muscle and inner ear, and that it exhibits synergistic genetic ..
  24. Coletta R, Christensen K, Reichenberger K, Lamb J, Micomonaco D, Huang L, et al. The Six1 homeoprotein stimulates tumorigenesis by reactivation of cyclin A1. Proc Natl Acad Sci U S A. 2004;101:6478-83 pubmed
    ..Here we show that the tissue-restricted cyclin A1 is a transcriptional target of the Six1 homeoprotein...
  25. Kondkar A, Azad T, Almobarak F, Kalantan H, Sultan T, Alsabaani N, et al. Polymorphism rs10483727 in the SIX1/SIX6 Gene Locus Is a Risk Factor for Primary Open Angle Glaucoma in a Saudi Cohort. Genet Test Mol Biomarkers. 2017;: pubmed publisher
    Variant rs10483727 in the SIX1/SIX6 locus has been significantly associated with primary open angle glaucoma (POAG) in multiple ethnic groups...
  26. Xu H, Zhang Y, Altomare D, Pena M, Wan F, Pirisi L, et al. Six1 promotes epithelial-mesenchymal transition and malignant conversion in human papillomavirus type 16-immortalized human keratinocytes. Carcinogenesis. 2014;35:1379-88 pubmed publisher
    b>Six1, a member of the Six family of homeodomain transcription factors, is overexpressed in various human cancers, and SIX1 overexpression is associated with tumor progression and metastasis...
  27. Sehic D, Karlsson J, Sandstedt B, Gisselsson D. SIX1 protein expression selectively identifies blastemal elements in Wilms tumor. Pediatr Blood Cancer. 2012;59:62-8 pubmed publisher
    ..A prominent exception was SIX1, being expressed predominantly in blastemal elements in 24/25 pediatric cases containing blastema...
  28. Kawasaki T, Takahashi M, Yajima H, Mori Y, Kawakami K. Six1 is required for mouse dental follicle cell and human periodontal ligament-derived cell proliferation. Dev Growth Differ. 2016;58:530-45 pubmed publisher
    ..We previously reported homeobox transcription factor Six1 expression in mouse DFCs. However, the role of Six1 in periodontal tissue development is largely unknown...
  29. Yan N, Cheng L, Cho K, Malik M, Xiao L, Guo C, et al. Postnatal onset of retinal degeneration by loss of embryonic Ezh2 repression of Six1. Sci Rep. 2016;6:33887 pubmed publisher
    ..in progressive photoreceptor degeneration throughout postnatal life, via derepression of fetal expression of Six1 and its targets...
  30. Brunmeir R, Wu J, Peng X, Kim S, Julien S, Zhang Q, et al. Comparative Transcriptomic and Epigenomic Analyses Reveal New Regulators of Murine Brown Adipogenesis. PLoS Genet. 2016;12:e1006474 pubmed publisher
    ..We also identify and subsequently validate PIM1, SIX1 and RREB1 as novel regulators promoting brown adipogenesis...
  31. Wei D, Ma X, Zhang S, Hong J, Gui L, Mei C, et al. Characterization of the promoter region of the bovine SIX1 gene: Roles of MyoD, PAX7, CREB and MyoG. Sci Rep. 2017;7:12599 pubmed publisher
    The SIX1 gene belongs to the family of six homeodomain transcription factors (TFs), that regulates the extracellular signal-regulated kinase 1/2 (ERK1/2) pathway and mediate skeletal muscle growth and regeneration...
  32. Wang L, Liu H. microRNA-188 is downregulated in oral squamous cell carcinoma and inhibits proliferation and invasion by targeting SIX1. Tumour Biol. 2016;37:4105-13 pubmed publisher
    ..Using fluorescence reporter assays, we confirmed that SIX1 was a direct target of miR-188 in OSCC cells. Transfection of miR-188 mimics downregulated SIX1 expression...
  33. Li Z, Tian T, Hu X, Zhang X, Nan F, Chang Y, et al. Six1 mediates resistance to paclitaxel in breast cancer cells. Biochem Biophys Res Commun. 2013;441:538-43 pubmed publisher
    Paclitaxel resistance remains a major challenge in the treatment of breast cancer. Six1 is a homeodomain-containing transcription factor invloved in the initiation, progression and metastasis of breast cancer...
  34. Filipova D, Walter A, Gaspar J, Brunn A, Linde N, Ardestani M, et al. Gene profiling of embryonic skeletal muscle lacking type I ryanodine receptor Ca(2+) release channel. Sci Rep. 2016;6:20050 pubmed publisher
    ..Additional qRT-PCR analysis revealed altered mRNA levels of the canonical muscle regulatory factors Six1, Six4, Pax7, MyoD, MyoG and MRF4 in mutant muscle, which is in line with the severe developmental retardation seen ..
  35. Cai B, Li Z, Ma M, Wang Z, Han P, Abdalla B, et al. LncRNA-Six1 Encodes a Micropeptide to Activate Six1 in Cis and Is Involved in Cell Proliferation and Muscle Growth. Front Physiol. 2017;8:230 pubmed publisher
    ..In our previous RNA-seq study (accession number GSE58755), we found that lncRNA-Six1 is an lncRNA that is differentially expressed between White Recessive Rock (WRR) and Xinghua (XH) chicken...
  36. Wiggs J, Yaspan B, Hauser M, Kang J, Allingham R, Olson L, et al. Common variants at 9p21 and 8q22 are associated with increased susceptibility to optic nerve degeneration in glaucoma. PLoS Genet. 2012;8:e1002654 pubmed publisher
    ..69 [95%CI 0.63-0.75], p?=?1.86×10?¹?), and the SIX1/SIX6 region on chromosome 14q23 (rs10483727 [A], OR?=?1.32 [95%CI 1.21-1.43], p?=?3.87×10?¹¹)...
  37. Daubas P, Duval N, Bajard L, Langa Vives F, Robert B, Mankoo B, et al. Fine-tuning the onset of myogenesis by homeobox proteins that interact with the Myf5 limb enhancer. Biol Open. 2015;4:1614-24 pubmed publisher
    ..Pax3 and Six1/4 transcription factors are essential activators of this enhancer, acting on a 145-bp core element...
  38. Nagel S, Meyer C, Kaufmann M, Drexler H, MacLeod R. Aberrant expression of homeobox gene SIX1 in Hodgkin lymphoma. Oncotarget. 2015;6:40112-26 pubmed publisher
    ..Here, we examined in HL homeobox gene SIX1 an additional regulator of this embryonal region mediating differentiation of placodal precursors...
  39. Zhao H, Xu Z, Qin H, Gao Z, Gao L. miR-30b regulates migration and invasion of human colorectal cancer via SIX1. Biochem J. 2014;460:117-25 pubmed publisher
    ..Furthermore, miR-30b was much lower in liver metastasis tissues than in CRCs. We validated SIX1 (SIX homeobox 1), a member of the SIX homeodomain family of transcription factors and an EMT (epithelial-..
  40. Wei D, Li A, Zhao C, Wang H, Mei C, Khan R, et al. Transcriptional Regulation by CpG Sites Methylation in the Core Promoter Region of the Bovine SIX1 Gene: Roles of Histone H4 and E2F2. Int J Mol Sci. 2018;19: pubmed publisher
    ..The SIX1 gene is thought to play a principal role in mediating skeletal muscle development...
  41. Yajima H, Kawakami K. Low Six4 and Six5 gene dosage improves dystrophic phenotype and prolongs life span of mdx mice. Dev Growth Differ. 2016;58:546-61 pubmed publisher
    ..We demonstrated previously the involvement of homeobox transcription factors, SIX1, SIX4 and SIX5, in the coordinated proliferation and differentiation of isolated satellite cells in vitro...
  42. Cui Q, Kong D, Li Z, Ahiable P, Wang K, Wu K, et al. Dachshund 1 is Differentially Expressed Between Male and Female Breast Cancer: A Matched Case-Control Study of Clinical Characteristics and Prognosis. Clin Breast Cancer. 2018;18:e875-e882 pubmed publisher
    ..prognosis were analyzed, and immunohistochemistry for androgen receptor (AR), dachshund 1 (DACH1), sine oculis 1 (SIX1), eyes absent 1, B-cell lymphoma-2, and p53 were performed on paraffin sections. MBC constituted 0...
  43. Kong J, Zhou X, Liu S, Jin T, Piao Y, Liu C, et al. Overexpression of sineoculis homeobox homolog 1 predicts poor prognosis of hepatocellular carcinoma. Int J Clin Exp Pathol. 2014;7:3018-27 pubmed
    High expression levels of the human sineoculis homeobox homolog 1 (SIX1) gene have been correlated with numerous human malignancies...
  44. Lerbs T, Bisht S, Schölch S, Pecqueux M, Kristiansen G, Schneider M, et al. Inhibition of Six1 affects tumour invasion and the expression of cancer stem cell markers in pancreatic cancer. BMC Cancer. 2017;17:249 pubmed publisher
    ..In this study, we focused on the evaluation of the transcription factor Six1 (Sine oculis 1)...
  45. Sato E, Williams M, Sanford J, Sen G, Nakama T, Imafuku S, et al. The parathyroid hormone family member TIP39 interacts with sarco/endoplasmic reticulum Ca2+ - ATPase activity by influencing calcium homoeostasis. Exp Dermatol. 2017;26:792-797 pubmed publisher
    ..model of DD and use this model to evaluate peptide therapy with tuberoinfundibular peptide of 39 residues (TIP39) to normalize calcium transport...
  46. Mosrati M, Hammami B, Rebeh I, Ayadi L, Dhouib L, Ben Mahfoudh K, et al. A novel dominant mutation in SIX1, affecting a highly conserved residue, result in only auditory defects in humans. Eur J Med Genet. 2011;54:e484-8 pubmed publisher
    ..Mutation in SIX1 is responsible also for DFNA23, a locus for non-syndromic HI...
  47. Blevins M, Towers C, Patrick A, Zhao R, Ford H. The SIX1-EYA transcriptional complex as a therapeutic target in cancer. Expert Opin Ther Targets. 2015;19:213-25 pubmed publisher
    ..Abnormal over-expression of SIX1 and EYA in adult tissue is associated with the initiation and progression of diverse tumor types...
  48. Boucher C, Carey N, Edwards Y, Siciliano M, Johnson K. Cloning of the human SIX1 gene and its assignment to chromosome 14. Genomics. 1996;33:140-2 pubmed
    The recently described murine homeobox genes, Six1 and Six2, which are expressed during development in limb tendons, have also been shown to be expressed in skeletal and smooth muscle, respectively...
  49. Riddiford N, Schlosser G. Six1 and Eya1 both promote and arrest neuronal differentiation by activating multiple Notch pathway genes. Dev Biol. 2017;431:152-167 pubmed publisher
    The transcription factor Six1 and its cofactor Eya1 are important regulators of neurogenesis in cranial placodes, activating genes promoting both a progenitor state, such as hes8, and neuronal differentiation, such as neurog1...
  50. Yang Q, Wang J, Li Z. [Differentially expressed genes between the human mandible- and ilium- derived mesenchymal cells]. Shanghai Kou Qiang Yi Xue. 2017;26:180-183 pubmed
    ..After the analysis from Gene MANIA database, the molecular networks of MSX1, MSX2, HAND2, SIX1, PITX2, OSR2, PAX3 and PRRX1 were built to show that these eight genes exhibited interactions, including co-..
  51. Wan F, Miao X, Quraishi I, Kennedy V, Creek K, Pirisi L. Gene expression changes during HPV-mediated carcinogenesis: a comparison between an in vitro cell model and cervical cancer. Int J Cancer. 2008;123:32-40 pubmed publisher
    ..Two novel genes were selected for further study: overexpression of SIX1 and GDF15, observed during in vitro progression in our model system, was confirmed in tissue arrays of cervical ..
  52. Suen A, Jefferson W, Wood C, Padilla Banks E, Bae Jump V, Williams C. SIX1 Oncoprotein as a Biomarker in a Model of Hormonal Carcinogenesis and in Human Endometrial Cancer. Mol Cancer Res. 2016;14:849-58 pubmed publisher
    The oncofetal protein sine oculis-related homeobox 1 (SIX1) is a developmental transcription factor associated with carcinogenesis in several human cancer types but has not been investigated in human endometrial cancer...
  53. Armat M, Oghabi Bakhshaiesh T, Sabzichi M, Shanehbandi D, Sharifi S, Molavi O, et al. The role of Six1 signaling in paclitaxel-dependent apoptosis in MCF-7 cell line. Bosn J Basic Med Sci. 2016;16:28-34 pubmed publisher
    ..Despite intensive research, mechanisms of resistance have not yet been fully elucidated. Six1 signaling has an important role in the expansion of progenitor cell populations during early embryogenesis...
  54. Hua L, Fan L, Aichun W, Yongjin Z, Qingqing C, Xiaojian W. Inhibition of Six1 promotes apoptosis, suppresses proliferation, and migration of osteosarcoma cells. Tumour Biol. 2014;35:1925-31 pubmed publisher
    Sineoculis homeobox homolog 1 (Six1) is one of the transcription factors that act as master regulators of development and is frequently dysregulated in cancers. However, the biological role of Six1 is not clear in osteosarcoma...
  55. Patrick A, Cabrera J, Smith A, Chen X, Ford H, Zhao R. Structure-function analyses of the human SIX1-EYA2 complex reveal insights into metastasis and BOR syndrome. Nat Struct Mol Biol. 2013;20:447-53 pubmed publisher
    b>SIX1 interacts with EYA to form a bipartite transcription factor essential for mammalian development. Loss of function of this complex causes branchio-oto-renal (BOR) syndrome, whereas re-expression of SIX1 or EYA promotes metastasis...
  56. Mimae T, Okada M, Hagiyama M, Miyata Y, Tsutani Y, Inoue T, et al. Upregulation of notch2 and six1 is associated with progression of early-stage lung adenocarcinoma and a more aggressive phenotype at advanced stages. Clin Cancer Res. 2012;18:945-55 pubmed publisher
    ..The transcription factors Notch2 and Six1 were upregulated in invasive cancer cells in all 11 minimally invasive adenocarcinomas...
  57. Yang Z, Feng Z, Gu J, Li X, Dong Q, Liu K, et al. microRNA-488 inhibits chemoresistance of ovarian cancer cells by targeting Six1 and mitochondrial function. Oncotarget. 2017;8:80981-80993 pubmed publisher
    ..Luciferase reporter assay showed that Six1 is a target of miR-488. We also found a negative association between Six1 and miR-488 in ovarian cancer tissues...
  58. Van Otterloo E, Li H, Jones K, Williams T. AP-2α and AP-2β cooperatively orchestrate homeobox gene expression during branchial arch patterning. Development. 2018;145: pubmed publisher
    ..of homeobox gene expression, with reduced levels of Emx, Msx and Dlx paralogs accompanied by an expansion of Six1 expression...
  59. L pez R os J, Tessmar K, Loosli F, Wittbrodt J, Bovolenta P. Six3 and Six6 activity is modulated by members of the groucho family. Development. 2003;130:185-95 pubmed
    ..These data indicate that both Tle1 and Aes participate in the molecular network that control eye development and are consistent with the view that both Six3 and Six6 act in combination with either Tle1 and/or Aes...
  60. Vivante A, Kleppa M, Schulz J, Kohl S, Sharma A, Chen J, et al. Mutations in TBX18 Cause Dominant Urinary Tract Malformations via Transcriptional Dysregulation of Ureter Development. Am J Hum Genet. 2015;97:291-301 pubmed publisher
    ..These data indicate that dominant-negative TBX18 mutations cause human CAKUT by interference with TBX18 transcriptional repression, thus implicating ureter smooth muscle cell development in the pathogenesis of human CAKUT. ..
  61. Gadd S, Huff V, Walz A, Ooms A, Armstrong A, Gerhard D, et al. A Children's Oncology Group and TARGET initiative exploring the genetic landscape of Wilms tumor. Nat Genet. 2017;49:1487-1494 pubmed publisher
    ..In addition to genes previously implicated in Wilms tumors (WT1, CTNNB1, AMER1, DROSHA, DGCR8, XPO5, DICER1, SIX1, SIX2, MLLT1, MYCN, and TP53), we identified mutations in genes not previously recognized as recurrently involved ..
  62. Hintze M, Prajapati R, Tambalo M, Christophorou N, Anwar M, Grocott T, et al. Cell interactions, signals and transcriptional hierarchy governing placode progenitor induction. Development. 2017;144:2810-2823 pubmed publisher
    In vertebrates, cranial placodes contribute to all sense organs and sensory ganglia and arise from a common pool of Six1/Eya2+ progenitors...
  63. Ou Z, Martin D, Bedoyan J, Cooper M, Chinault A, Stankiewicz P, et al. Branchiootorenal syndrome and oculoauriculovertebral spectrum features associated with duplication of SIX1, SIX6, and OTX2 resulting from a complex chromosomal rearrangement. Am J Med Genet A. 2008;146A:2480-9 pubmed publisher
    ..3-q24.3, and designated as branchiootic syndrome 3 (BOS3). Interestingly, mutations in SIX1 have been reported in patients with BOR/BOS3...
  64. Yang J, Li G, Zhang K. Pro-survival effects by NF-?B, Akt and ERK(1/2) and anti-apoptosis actions by Six1 disrupt apoptotic functions of TRAIL-Dr4/5 pathway in ovarian cancer. Biomed Pharmacother. 2016;84:1078-1087 pubmed publisher
    ..b>Six1, a homeobox transcription factor, had higher expression in SKOV-3ip1 and A2780 cells than in OVCAR-3 cells...
  65. Xu H, Zhang Y, Peña M, Pirisi L, Creek K. Six1 promotes colorectal cancer growth and metastasis by stimulating angiogenesis and recruiting tumor-associated macrophages. Carcinogenesis. 2017;38:281-292 pubmed publisher
    The homeoprotein Six1 is overexpressed in many human cancers and is associated with increased tumor progression and metastasis...
  66. Li Z, Tian T, Hu X, Zhang X, Li L, Nan F, et al. Targeting Six1 by lentivirus-mediated RNA interference inhibits colorectal cancer cell growth and invasion. Int J Clin Exp Pathol. 2014;7:631-9 pubmed
    The Six1 homeodomain protein is a developmental transcription factor that has been implicated in tumor onset and progression...
  67. Xu Dong S, Zan S, Shui er Z, Li na T, Wen xi Y, Feng L, et al. Expression of Ezrin correlates with lung metastasis in Chinese patients with osteosarcoma. Clin Invest Med. 2009;32:E180-8 pubmed
    To determine the prognostic value of the expression of Ezrin, CD44 and Six1 genes in osteosarcoma tissues of Chinese patients...
  68. Sang J, Jia L, Zhao B, Wang H, Zhang N, Wang N. Association of three single nucleotide polymorphisms at the SIX1-SIX6 locus with primary open angle glaucoma in the Chinese population. Sci China Life Sci. 2016;59:694-9 pubmed publisher
    ..genetic association of three single nucleotide polymorphisms (SNPs; rs10483727, rs33912345, and rs146737847) at the SIX1-SIX6 locus with primary open angle glaucoma (POAG) in the Chinese population...
  69. Spreafico F, Ciceri S, Gamba B, Torri F, Terenziani M, Collini P, et al. Chromosomal anomalies at 1q, 3, 16q, and mutations of SIX1 and DROSHA genes underlie Wilms tumor recurrences. Oncotarget. 2016;7:8908-15 pubmed publisher
    ..of primary/recurrent WTs through whole-genome SNP arrays, and investigated known WT-associated genes, including SIX1, SIX2 and micro RNA processor genes, whose mutations have been recently proposed as associated with worse outcome...
  70. Matsuzaki S, Hosoya M, Okano H, Fujioka M, Ogawa K. Expression pattern of EYA4 in the common marmoset (Callithrix jacchus) cochlea. Neurosci Lett. 2018;662:185-188 pubmed publisher
    ..EYA4 expression in the hair cells, supporting cells and neurons was co-localized with sine oculis homeobox-SIX1, a transcription factor essential for the transcriptional activity of EYA4...
  71. Ruf R, Berkman J, Wolf M, Nurnberg P, Gattas M, Ruf E, et al. A gene locus for branchio-otic syndrome maps to chromosome 14q21.3-q24.3. J Med Genet. 2003;40:515-9 pubmed
  72. Walz A, Ooms A, Gadd S, Gerhard D, Smith M, Guidry Auvil J, et al. Recurrent DGCR8, DROSHA, and SIX homeodomain mutations in favorable histology Wilms tumors. Cancer Cell. 2015;27:286-97 pubmed publisher
    ..single-nucleotide substitution/deletion mutations in favorable histology Wilms tumors (FHWTs) to occur within SIX1/2 (7% of 534 tumors) and microRNA processing genes (miRNAPGs) DGCR8 and DROSHA (15% of 534 tumors)...
  73. Li B, Xu L, Hong N, Chen S, Xu R. In Silico Analyses Reveal the Relationship Between SIX1/EYA1 Mutations and Conotruncal Heart Defects. Pediatr Cardiol. 2018;39:176-182 pubmed publisher
    ..Previous studies indicated that transcriptional complex SIX1/EYA1 may contribute to SHF development, and SIX1/EYA1 knockout mice exhibited a series of conotruncal malformations...
  74. Sanggaard K, Rendtorff N, Kjaer K, Eiberg H, Johnsen T, Gimsing S, et al. Branchio-oto-renal syndrome: detection of EYA1 and SIX1 mutations in five out of six Danish families by combining linkage, MLPA and sequencing analyses. Eur J Hum Genet. 2007;15:1121-31 pubmed
    ..BOR is genetically heterogeneous and caused by mutations in EYA1 (8q13.3), SIX1 (14q23.1), SIX5 (19q13.3) and in an unidentified gene on 1q31...
  75. Smith A, Iwanaga R, Drasin D, Micalizzi D, Vartuli R, Tan A, et al. The miR-106b-25 cluster targets Smad7, activates TGF-? signaling, and induces EMT and tumor initiating cell characteristics downstream of Six1 in human breast cancer. Oncogene. 2012;31:5162-71 pubmed publisher
    ..The metastatic regulator, Six1, was recently shown to mediate this switch, providing a novel means to explain this elusive 'TGF-? paradox'...