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

Vervoort, Stephin J.; Lourenço, Ana Rita; Boxtel, Ruben van; Coffer, Paul J.

doi:10.1371/journal.pone.0053238

Cited by 82 publications

(87 citation statements)

References 43 publications

(56 reference statements)

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“…That the computational model at the core of ISMARA, i.e., motif activity response analysis, is a powerful method for reconstructing regulatory interactions from high-throughput data has already been demonstrated, not only in its original application (The FANTOM Consortium et al 2009), but in a substantial number of recent studies across a wide range of mammalian systems (Summers et al 2010;Aceto et al 2012;Arner et al 2012;Arnold et al 2012b;The FANTOM Consortium et al 2012;Hasegawa et al 2012;Pérez-Schindler et al 2012;Eisele et al 2013;Meier-Abt et al 2013;Tiwari et al 2013a,b;Vervoort et al 2013). In each of these studies, MARA successfully inferred key regulators and their regulatory interactions ab initio.…”

Section: Discussionmentioning

confidence: 99%

“…Thus, whereas many laboratories are now routinely producing high-throughput data sets, and methodologies for analyzing such data have been described in the literature, the vast majority of groups that produce data have to develop collaborations with expert computational groups to apply these methods. Indeed, in recent years MARA has been applied to a large range of mammalian systems studied by various experimental collaborators and experimentally validated predicted regulatory circuitry in these systems (Summers et al 2010;Aceto et al 2012;Arner et al 2012;Hasegawa et al 2012;Pérez-Schindler et al 2012;Suzuki et al 2012;Eisele et al 2013;Meier-Abt et al 2013;Tiwari et al 2013a,b;Vervoort et al 2013). Although these studies further validated the power of the method, they required a considerable investment of time and effort for the analysis of each new data set.…”

Section: [Supplemental Materials Is Available For This Article]mentioning

confidence: 99%

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ISMARA: automated modeling of genomic signals as a democracy of regulatory motifs

et al. 2014

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Accurate reconstruction of the regulatory networks that control gene expression is one of the key current challenges in molecular biology. Although gene expression and chromatin state dynamics are ultimately encoded by constellations of binding sites recognized by regulators such as transcriptions factors (TFs) and microRNAs (miRNAs), our understanding of this regulatory code and its context-dependent read-out remains very limited. Given that there are thousands of potential regulators in mammals, it is not practical to use direct experimentation to identify which of these play a key role for a particular system of interest. We developed a methodology that models gene expression or chromatin modifications in terms of genome-wide predictions of regulatory sites and completely automated it into a web-based tool called ISMARA (Integrated System for Motif Activity Response Analysis). Given only gene expression or chromatin state data across a set of samples as input, ISMARA identifies the key TFs and miRNAs driving expression/chromatin changes and makes detailed predictions regarding their regulatory roles. These include predicted activities of the regulators across the samples, their genome-wide targets, enriched gene categories among the targets, and direct interactions between the regulators. Applying ISMARA to data sets from well-studied systems, we show that it consistently identifies known key regulators ab initio. We also present a number of novel predictions including regulatory interactions in innate immunity, a master regulator of mucociliary differentiation, TFs consistently disregulated in cancer, and TFs that mediate specific chromatin modifications.

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Section: Discussionmentioning

confidence: 99%

Section: [Supplemental Materials Is Available For This Article]mentioning

confidence: 99%

ISMARA: automated modeling of genomic signals as a democracy of regulatory motifs

et al. 2014

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“…SOX4 and SOX9 are known regulators of these pathways in cancer and development (Bhattaram et al, 2010;Delous et al, 2012;Kuwahara et al, 2012;Manfroid et al, 2012;Moreno, 2010;Scharer et al, 2009;Song et al, 2013;Vervoort et al, 2013), raising the possibility that SOX factors control biliary development by modulating the response to intercellular signaling. To -14 -address this hypothesis, we investigated the expression of signaling markers in SOX factor-deficient livers.…”

Section: Sox4 and Sox9 Control Signaling Pathways Involved In Biliarymentioning

confidence: 99%

Transcription factors SOX4 and SOX9 cooperatively control development of bile ducts

Poncy

Antoniou

Cordi

et al. 2015

Developmental Biology

100

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In developing liver, cholangiocytes derive from the hepatoblasts and organize to form the bile ducts. Earlier work has shown that the SRY-related High Mobility Group box transcription factor 9 (SOX9) is transiently required for bile duct development, raising the question of the potential involvement of other SOX family members in biliary morphogenesis. Here we identify SOX4 as a new regulator of cholangiocyte development. Liver-specific inactivation of SOX4, combined or not with inactivation of SOX9, affects cholangiocyte differentiation, apico-basal polarity and bile duct formation. Both factors cooperate to control the expression of mediators of the Transforming Growth Factor-β, Notch, and Hippo-Yap signaling pathways, which are required for normal development of the bile ducts. In addition, SOX4 and SOX9 control formation of primary cilia, which are known signaling regulators. The two factors also stimulate secretion of laminin α5, an extracellular matrix component promoting bile duct maturation. We conclude that SOX4 is a new regulator of liver development and that it exerts a pleiotropic control on bile duct development in cooperation with SOX9.

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“…24,25 In addition, SOX4 was shown to regulate several key signaling pathways in cancer cells such as the Wnt pathway, Notch1 pathway, and P53 pathway. 26,27 Of note, SOX4 could serve as a master mediator in EMT process by regulating EMT marker, 28,29 which is a critical step in tumor progression and metastasis. 30 In this study, SOX4 was identified as a direct target of miR-25 by a luciferase reporter assay, quantitative reverse transcription polymerase chain reaction (qRT-PCR), and western blot.…”

Section: Discussionmentioning

confidence: 99%

MicroRNA-25 suppresses proliferation, migration, and invasion of osteosarcoma by targeting SOX4

Chen

Liu

et al. 2017

Tumour Biol.

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Altered expression of the miR-25 has been implicated in many human malignant progression as oncogene or tumor suppressor. However, the precise role of miR-25 in osteosarcoma progression remains largely unclear. This study aimed to investigate the role and underlying mechanism of miR-25 in osteosarcoma. In this study, we demonstrated that miR-25 was significantly downregulated in osteosarcoma cell lines and tissues and that lower miR-25 was associated with advanced tumor-node-metastasis stage and lymph node metastasis. Then, we found that introduction of miR-25 significantly suppressed the proliferation, colony formation, migration, and invasion of osteosarcoma cells in vitro and retarded tumor growth in vivo. Further studies indicated that the epithelial-mesenchymal transition-related transcription factor, SOX4 (SRY-related high-mobility group box 4), was a direct target gene of miR-25, evidenced by bioinformatics analysis predicted and luciferase reporter assay. Furthermore, miR-25 could decrease the expression of SOX4 levels and inhibited epithelial-mesenchymal transition process. The levels of miR-25 were inversely correlated with those of SOX4 expression in osteosarcoma tissues. SOX4 overexpression rescued miR-25-induced suppression of proliferation, migration, and invasion of osteosarcoma cells. Taken together, these results suggest that miR-25 functions as a tumor suppressor in the progression of osteosarcoma by repressing SOX4.

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

Cited by 82 publications

References 43 publications

ISMARA: automated modeling of genomic signals as a democracy of regulatory motifs

ISMARA: automated modeling of genomic signals as a democracy of regulatory motifs

Transcription factors SOX4 and SOX9 cooperatively control development of bile ducts

MicroRNA-25 suppresses proliferation, migration, and invasion of osteosarcoma by targeting SOX4

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