Cell Fate Determination Factor DACH1 Inhibits c-Jun–induced Contact-independent Growth

Wu, Kongming; Liu, Manran; Li, An‐Ping; Donninger, Howard; Rao, Mahadev; Jiao, Xuanmao; Lisanti, Michael P.; Cvekl, Aleš; Birrer, Michael J.; Pestell, Richard G.

doi:10.1091/mbc.e06-09-0793

Cited by 72 publications

(86 citation statements)

References 66 publications

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“…As far as we know, this is the first study showing loss of DACH1 gene function in tumor cells at the genomic level. Our observation supports recent studies indicating that DACH1 scarcely expressed in tumor-initiating cells and such low expression correlated with poor prognosis of breast cancers (17,18,47). We showed that DACH1 expression decreases proliferation of glioma cells and suppresses tumorigenicity through inhibition of bFGF-dependent spheroid formation.…”

Section: Dach1-spanning Region Is Indicated As a Target Of Copy Numbesupporting

confidence: 92%

“…DACH1 is structurally related to c-Ski and SnoN, which act as transcriptional repressors of the transforming growth factor-β (TGF-β) signaling pathway through the interaction with Smad proteins (16). Previous studies showed that human DACH1 inhibited TGF-β signaling through repressing cyclin D1 (CCND1) expression and decreased proliferation of breast cancer cells (17,18). We examined whether DACH1 expression affected TGF-β signaling in glioma cells.…”

Section: Dach1 Inhibits Formation Of Tumor-initiating Spheroids Of Glmentioning

confidence: 99%

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Homozygously deleted gene DACH1 regulates tumor-initiating activity of glioma cells

Watanabe

Ogiwara

Ehata³

et al. 2011

Proc. Natl. Acad. Sci. U.S.A.

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Loss or reduction in function of tumor suppressor genes contributes to tumorigenesis. Here, by allelic DNA copy number analysis using single-nucleotide polymorphism genotyping array and mass spectrometry, we report homozygous deletion in glioblastoma multiformes at chromosome 13q21, where DACH1 gene is located. We found decreased cell proliferation of a series of glioma cell lines by forced expression of DACH1. We then generated U87TR-Da glioma cells, where DACH1 expression could be activated by exposure of the cells to doxycycline. Both ex vivo cellular proliferation and in vivo growth of s.c. transplanted tumors in mice are reduced in U87TR-Da cells with DACH1 expression (U87-DACH1-high), compared with DACH1-nonexpressing U87TR-Da cells (U87-DACH1-low). U87-DACH1-low cells form spheroids with CD133 and Nestin expression in serum-free medium but U87-DACH1-high cells do not. Compared with spheroid-forming U87-DACH1-low cells, adherent U87-DACH1-high cells display lower tumorigenicity, indicating DACH1 decreases the number of tumor-initiating cells. Gene expression analysis and chromatin immunoprecipitation assay reveal that fibroblast growth factor 2 (FGF2/bFGF) is transcriptionally repressed by DACH1, especially in cells cultured in serum-free medium. Exogenous bFGF rescues spheroid-forming activity and tumorigenicity of the U87-DACH1-high cells, suggesting that loss of DACH1 increases the number of tumor-initiating cells through transcriptional activation of bFGF. These results illustrate that DACH1 is a distinctive tumor suppressor, which does not only suppress growth of tumor cells but also regulates bFGF-mediated tumor-initiating activity of glioma cells.neural differentiation | gliomagenesis

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Section: Dach1-spanning Region Is Indicated As a Target Of Copy Numbesupporting

confidence: 92%

Section: Dach1 Inhibits Formation Of Tumor-initiating Spheroids Of Glmentioning

confidence: 99%

Homozygously deleted gene DACH1 regulates tumor-initiating activity of glioma cells

Watanabe

Ogiwara

Ehata³

et al. 2011

Proc. Natl. Acad. Sci. U.S.A.

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“…DNA synthesis was analyzed by [ 3 H] thymidine (TdR) incorporation as previously described. 31,32 S phase was analyzed by flow cytometry. The Annexin V-PE apoptosis detection kit (BD Biosciences, Franklin, NJ) was used according to the manufacturer's protocol, followed by flow cytometry.…”

Section: Mtt Flow Cytometric Analysis Dna Synthesis Analysis and Amentioning

confidence: 99%

Nuclear Factor-κB Enhances ErbB2-Induced Mammary Tumorigenesis and Neoangiogenesis in Vivo

Liu

Willmarth

et al. 2009

The American Journal of Pathology

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“…DACH1 blocks c-Jun-induced DNA synthesis, reverts the H-Ras and c-Myc-induced oncogenic phenotype in the immortalized human breast epithelial cell line, and inhibits breast tumor metastasis in mice (2,7). Although DACH1 is thought to regulate gene expression by complexing with DNAbinding transcription factors including Six, Jun, and Smad4 (2,(8)(9)(10), no sequence specific DNA binding of DACH1 has been identified so far to our knowledge.…”

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confidence: 99%

Attenuation of Forkhead signaling by the retinal determination factor DACH1

Zhou

Wang

et al. 2010

Proc. Natl. Acad. Sci. U.S.A.

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The Drosophila Dachshund (Dac) gene, cloned as a dominant inhibitor of the hyperactive growth factor mutant ellipse, encodes a key component of the retinal determination gene network that governs cell fate. Herein, cyclic amplification and selection of targets identified a DACH1 DNA-binding sequence that resembles the FOX (Forkhead box-containing protein) binding site. Genome-wide in silico promoter analysis of DACH1 binding sites identified gene clusters populating cellular pathways associated with the cell cycle and growth factor signaling. ChIP coupled with high-throughput sequencing mapped DACH1 binding sites to corresponding gene clusters predicted in silico and identified as weight matrix resembling the cyclic amplification and selection of targets-defined sequence. DACH1 antagonized FOXM1 target gene expression, promoter occupancy in the context of local chromatin, and contactindependent growth. Attenuation of FOX function by the cell fate determination pathway has broad implications given the diverse role of FOX proteins in cellular biology and tumorigenesis.cell fate determination | Forkhead protein | transcription factor | tumor suppressor | dachshund homolog 1

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Cell Fate Determination Factor DACH1 Inhibits c-Jun–induced Contact-independent Growth

Cited by 72 publications

References 66 publications

Homozygously deleted gene DACH1 regulates tumor-initiating activity of glioma cells

Homozygously deleted gene DACH1 regulates tumor-initiating activity of glioma cells

Nuclear Factor-κB Enhances ErbB2-Induced Mammary Tumorigenesis and Neoangiogenesis in Vivo

Attenuation of Forkhead signaling by the retinal determination factor DACH1

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