Singular value decomposition-based regression identifies activation of endogenous signaling pathways in vivo

Liu, Zhandong; Wang, Min; Alvarez, James V.; Bonney, Megan; Chen, Chien-Chung; D’Cruz, Celina M.; Pan, Tien-Chi; Tadesse, Mahlet G.; Chodosh, Lewis A.

doi:10.1186/gb-2008-9-12-r180

Cited by 12 publications

(7 citation statements)

References 39 publications

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“…This interrogates transcription factor DNA binding site motifs to determine the transcription factors driving gene expression changes [13]. We used MARA to analyse two independent publicly available datasets of TGF-β treated mouse and human mammary epithelial cells (GSE13986 and GSE28448) [14], [15]. Despite the lack of a specific SOX4 binding motif present in the software, MARA analysis of both HMLE-Tert/Ras cells and normal murine mammary gland (NMuMG) cells treated with TGF-β for 24 h revealed a significant increase in the regulation of genes possessing a SOX binding motif, as exemplified by SOX2 (Fig.…”

Section: Resultsmentioning

confidence: 99%

SOX4 Mediates TGF-β-Induced Expression of Mesenchymal Markers during Mammary Cell Epithelial to Mesenchymal Transition

et al. 2013

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The epithelial to mensenchymal transition program regulates various aspects of embryonic development and tissue homeostasis, but aberrant activation of this pathway in cancer contributes to tumor progression and metastasis. TGF-β potently induces an epithelial to mensenchymal transition in cancers of epithelial origin by inducing transcriptional changes mediated by several key transcription factors. Here, we identify the developmental transcription factor SOX4 as a transcriptional target of TGF-β in immortalized human mammary epithelial cells. SOX4 expression and activity are rapidly induced in the early stages of the TGF-β-induced epithelial to mensenchymal transition. We demonstrate that conditional activation of Sox4 is sufficient to induce the expression of N-cadherin and additional mesenchymal markers including vimentin and fibronectin, but fails to induce complete EMT as no changes are observed in the expression of E-cadherin and β-catenin. Moreover, shRNA-mediated knockdown of SOX4 significantly delays TGF-β-induced mRNA and protein expression of mesenchymal markers. Taken together, these data suggest that TGF-β-mediated increased expression of SOX4 is required for the induction of a mesenchymal phenotype during EMT in human mammary epithelial cells.

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Section: Resultsmentioning

confidence: 99%

SOX4 Mediates TGF-β-Induced Expression of Mesenchymal Markers during Mammary Cell Epithelial to Mesenchymal Transition

et al. 2013

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“…Van de Waterbeemd et al (40) used this PCA method to study the optimal harvest point in bacterial vaccine production, and Liu et al (41) described the detection of endogenous signaling activation pathways by an oncogenic stimulus. Here we show yet another novel facet of PCA method to distinguish between gene expression pattern of SCD and DPSCs.…”

Section: Discussionmentioning

confidence: 99%

Inherent Differential Propensity of Dental Pulp Stem Cells Derived from Human Deciduous and Permanent Teeth

Govindasamy¹,

Abdullah

Ronald

et al. 2010

Journal of Endodontics

146

126

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“…Transcriptional profiling has been used widely to improve our understanding of the molecular basis of cancer phenotypes (Miller et al , ; Bild et al , ; Huang et al , ; Langenau et al , ; Rhodes et al , ; Liu et al , ; Waddell et al , ; Wong et al , ; Barbie et al , ; Ooi et al , ; Singh et al , ; Zhang et al , ). In normal cells, gene expression levels reflect functional germline genetic (and epigenomic) variation and thus may be useful as a surrogate for germline variation.…”

Section: Introductionmentioning

confidence: 99%

Integrative analyses reveal signaling pathways underlying familial breast cancer susceptibility

Piccolo

Hoffman

Conner

et al. 2016

Molecular Systems Biology

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The signaling events that drive familial breast cancer (FBC) risk remain poorly understood. While the majority of genomic studies have focused on genetic risk variants, known risk variants account for at most 30% of FBC cases. Considering that multiple genes may influence FBC risk, we hypothesized that a pathway‐based strategy examining different data types from multiple tissues could elucidate the biological basis for FBC. In this study, we performed integrated analyses of gene expression and exome‐sequencing data from peripheral blood mononuclear cells and showed that cell adhesion pathways are significantly and consistently dysregulated in women who develop FBC. The dysregulation of cell adhesion pathways in high‐risk women was also identified by pathway‐based profiling applied to normal breast tissue data from two independent cohorts. The results of our genomic analyses were validated in normal primary mammary epithelial cells from high‐risk and control women, using cell‐based functional assays, drug‐response assays, fluorescence microscopy, and Western blotting assays. Both genomic and cell‐based experiments indicate that cell–cell and cell–extracellular matrix adhesion processes seem to be disrupted in non‐malignant cells of women at high risk for FBC and suggest a potential role for these processes in FBC development.

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Singular value decomposition-based regression identifies activation of endogenous signaling pathways in vivo

Cited by 12 publications

References 39 publications

SOX4 Mediates TGF-β-Induced Expression of Mesenchymal Markers during Mammary Cell Epithelial to Mesenchymal Transition

SOX4 Mediates TGF-β-Induced Expression of Mesenchymal Markers during Mammary Cell Epithelial to Mesenchymal Transition

Inherent Differential Propensity of Dental Pulp Stem Cells Derived from Human Deciduous and Permanent Teeth

Integrative analyses reveal signaling pathways underlying familial breast cancer susceptibility

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