LASAGNA-Search: an Integrated Web Tool for Transcription Factor Binding Site Search and Visualization

Lee, Chih; Huang, Chun-Hsi

doi:10.2144/000113999

Cited by 113 publications

(84 citation statements)

References 48 publications

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“…24 It can be speculated thus, speculate that the unexpected lack of the C1q protein observed in neuT-C3KO tumors may be due to the lack of hypoxic-induced C1q mRNA transcription. Indeed, using the LASAGNA-Search tool 38 (http://biogrid.engr.uconn.edu/lasagna_search/) to perform binding sites searches on mouse C1q promoter, we confirmed the presence of binding sites specific for the transcriptional factors RelA, 39 Meis-1a, 40 AhR 41 , and Arnt, 42 known to be present on human C1q promoter and linked to hypoxia (GeneCards Ò , Human Gene Data base; http://www. genecards.org/cgi-bin/carddisp.pl?gene D C1QAandkeywords D c1qa).…”

Section: Discussionmentioning

confidence: 67%

The non-inflammatory role of C1q during Her2/neu-driven mammary carcinogenesis

et al. 2016

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There is an ever increasing amount of evidence to support the hypothesis that complement C1q, the first component of the classical complement pathway, is involved in the regulation of cancer growth, in addition to its role in fighting infections. It has been demonstrated that C1q is expressed in the microenvironment of various types of human tumors, including breast adenocarcinomas. This study compares carcinogenesis progression in C1q deficient (neuT-C1KO) and C1q competent neuT mice in order to investigate the role of C1q in mammary carcinogenesis. Significantly accelerated autochthonous neu C carcinoma progression was paralleled by accelerated spontaneous lung metastases occurrence in C1q deficient mice. Surprisingly, this effect was not caused by differences in the tumor-infiltrating cells or in the activation of the complement classical pathway, since neuT-C1KO mice did not display a reduction in C3 fragment deposition at the tumor site. By contrast, a significant higher number of intratumor blood vessels and a decrease in the activation of the tumor suppressor WW domain containing oxidoreductase (WWOX) were observed in tumors from neuT-C1KO as compare with neuT mice. In parallel, an increase in Her2/neu expression was observed on the membrane of tumor cells. Taken together, our findings suggest that C1q plays a direct role both on halting tumor angiogenesis and on inducing apoptosis in mammary cancer cells by coordinating the signal transduction pathways linked to WWOX and, furthermore, highlight the role of C1q in mammary tumor immune surveillance regardless of complement system activation.Abbreviations: BALB-C1KO, BALB/c mice deficient for the C1qA; BALB-C3KO, BALB/c mice deficient for C3; C1KO, C1q deficient; C1qR, C1q receptor; CR3, complement receptor 3; EMT, epithelial-to-mesenchymal transition; KLRK1 or NKG2D, killer cell lectin-like receptor subfamily K, member 1; MDCS, myeloid-derived suppressor cells; neuT, rat Her2/neu transgenic; neuT-BKO mice, neuT mice deficient in antibody production; neuT-C1KO mice, neuT mice deficient for the C1qA molecule; neuT-C3KO mice, neuT mice deficient for the C3 molecule; NK, natural killer; pWWOX, phospho WWOX; Treg, T regulatory; WWOX, WW domain containing oxidoreductase

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Section: Discussionmentioning

confidence: 67%

The non-inflammatory role of C1q during Her2/neu-driven mammary carcinogenesis

et al. 2016

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“…TCF4 binding sites at -1,000 bp upstream of the APCDD1 gene were analyzed in silico using the publicly available programs PROMO, LASAGNA and JASPAR (14)(15)(16)(17). ChIP assays using a ChIP kit (Abcam, Cambridge, MA, USA) were performed according to the manufacturer's protocol.…”

Section: Introductionmentioning

confidence: 99%

APC downregulated 1 inhibits breast cancer cell invasion by inhibiting the canonical WNT signaling pathway

Cho

2017

Oncology Letters

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Abstract. Canonical WNT signaling promotes breast cancer progression. Although APC downregulated 1 (APCDD1) may inhibit canonical WNT signaling, its role in breast cancer remains to be fully understood. The present study demonstrated that APCDD1 suppressed in vitro breast cancer growth and metastasis by inhibiting canonical WNT signaling. The present study demonstrated that APCDD1 expression was negatively associated with breast cancer cell invasion, which was consistent with previous studies that indicated that APCDD1 expression was decreased in invasive ductal carcinoma compared with that in ductal carcinoma in situ. Furthermore, APCDD1 expression was negatively associated with nuclear β-catenin expression and transcription factor/lymphoid enhancer binding factor 1 transcriptional activity in the present study. Silencing APCDD1 in non-invasive breast cancer cells using lentiviral APCDD1 short hairpin RNAs enhanced migration and invasion, which may be mediated by canonical WNT signaling, whereas the overexpression of human influenza hemagglutinin-tagged APCDD1 in invasive breast cancer cells repressed these properties. Therefore, the present study suggested that APCDD1 regulated breast cancer progression by targeting canonical WNT signaling and modulating breast cancer cell invasion. IntroductionThe WNT signaling pathway is associated with numerous biological events, including embryonic development and adult tissue homeostasis. Therefore, abnormal WNT signaling is associated with diseases, including certain types of cancer (1,2). WNTs activate the canonical and non-canonical signaling pathways, which are mutually exclusive. The canonical WNT signaling pathway triggers β-catenin-dependent transcriptional regulation, whereas the non-canonical WNT signaling pathway activates the β-catenin-independent signaling pathway (1,2).The canonical WNT signaling pathway regulates normal breast development, and its deregulation is associated with breast cancer progression (3,4). WNTs aid in the generation of the canonical WNT signaling pathway by binding to the coreceptors LDL receptor-related protein (LRP)5/6 and frizzled on the cell surface, and activating the β-catenin/t-cell factor (TCF) complex (2). Overexpression of Wnt1, which may be induced by the integration of the mouse mammary tumor virus, triggers mammary tumor development (5,6). Autocrine WNT signaling regulates mammary epithelial cell fate by regulating renewal and the epithelial-to-mesenchymal transition (EMT), thereby affecting tumorigenesis and metastasis in a deregulated signaling state (7,8). Accordingly, the WNT-activated β-catenin/TCF complex potentiates breast cancer metastasis by altering the expression of genes associated with EMT (9,10).Previous studies have revealed multiple inhibitors of the canonical WNT signaling pathway, including secreted frizzled-related protein (SFRP), dickkopf (DKK), and WNT inhibitory factor (WIF) (2,11). In addition, APC downregulated 1 (APCDD1) may inhibit the canonical WNT signaling pathway by directly binding WNT3A and L...

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“…Putative transcription factor binding sites were identified using the LASAGNAsearch web tool. 35 Flow cytometry Cultured B-cell lines were harvested and 1310 6 cells washed twice with cold staining buffer (PBS containing 5% FBS) at 300g for 5 min at 4 uC. Cells were resuspended in 80 mL staining buffer and incubated with 20 ml of PE-conjugated mouse antihuman CD21 antibody (555422; BD Biosciences, San Jose, CA, USA) or PE-conjugated mouse IgG1k isotype control (BD Biosciences, 551436), for 20 min.…”

Section: Identification Of Putative Core Promoter Elementsmentioning

confidence: 99%

“…25 Bioinformatics were generated with LASAGNE-Search 2.0 35 and site-directed mutagenesis was performed using the QuikChange mutagenesis kit (Stratagene, La Jolla, CA, USA). Plasmid DNA was prepared using the EndoFree Plasmid Maxi kit (QIAGEN, Valencia, CA, USA) followed by transient transfection with the Amaxa Nucleofector Device and Cell Line Nucleofector Solution V (Lonza, Basel, Switzerland).…”

Section: Transfection and Quantitation Of Promoter Activitymentioning

confidence: 99%

Focused transcription from the human CR2/CD21 core promoter is regulated by synergistic activity of TATA and Initiator elements in mature B cells

et al. 2015

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Complement receptor 2 (CR2/CD21) is predominantly expressed on the surface of mature B cells where it forms part of a coreceptor complex that functions, in part, to modulate B-cell receptor signal strength. CR2/CD21 expression is tightly regulated throughout B-cell development such that CR2/CD21 cannot be detected on pre-B or terminally differentiated plasma cells. CR2/CD21 expression is upregulated at B-cell maturation and can be induced by IL-4 and CD40 signaling pathways. We have previously characterized elements in the proximal promoter and first intron of CR2/CD21 that are involved in regulating basal and tissue-specific expression. We now extend these analyses to the CR2/CD21 core promoter. We show that in mature B cells, CR2/CD21 transcription proceeds from a focused TSS regulated by a non-consensus TATA box, an initiator element and a downstream promoter element. Furthermore, occupancy of the general transcriptional machinery in pre-B versus mature B-cell lines correlate with CR2/CD21 expression level and indicate that promoter accessibility must switch from inactive to active during the transitional B-cell window.

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LASAGNA-Search: an Integrated Web Tool for Transcription Factor Binding Site Search and Visualization

Cited by 113 publications

References 48 publications

The non-inflammatory role of C1q during Her2/neu-driven mammary carcinogenesis

The non-inflammatory role of C1q during Her2/neu-driven mammary carcinogenesis

APC downregulated 1 inhibits breast cancer cell invasion by inhibiting the canonical WNT signaling pathway

Focused transcription from the human CR2/CD21 core promoter is regulated by synergistic activity of TATA and Initiator elements in mature B cells

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