TFCP2c/LSF/LBP-1c is required for Snail1-induced fibronectin gene expression

Porta-de-la-Riva, Montserrat; Stanisavljević, Jelena; Curto, Josué; Francı́, Clara; Dı́az, Vı́ctor M.; Herreros, Antonio Garcı́a de; Baulida, Josep

doi:10.1042/bj20102057

Cited by 19 publications

(13 citation statements)

References 22 publications

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“…Our findings also showed that the core promoter was found from the human FN1 promoter region (−2000 to +200), and contained the putative regulatory motifs (CNRG-N 5–6 -CNRG/C). Inconsistent with the previous report [ 13 ], we found the TFCP2 regulation on FN1 through the same motifs. This further illustrates that TFCP2 regulates FN1 across different cell systems.…”

Section: Discussionsupporting

confidence: 89%

“…This further illustrates that TFCP2 regulates FN1 across different cell systems. Porta-de-la-Riva et al [ 13 ] found that FN1 was up-regulated upon EMT induction by Snail1 in normal development, then TFCP2 was found to bind the FN1 proximal promoter, which responses to Snail1. In our paper, FN1 was selected from ChIP on chip and array results of TFCP2 in cancer (HCC), we used a series of 5′-deletion fragments of the FN1 promoter (~2 kb region) to locate the responsive minimal promoter to TFCP2 and found involvement of TFCP2 in migration, as mediated through its direct upregulation of FN1.…”

Section: Discussionmentioning

confidence: 99%

“…The transcription factor CP2 (TFCP2) has been shown to regulate diverse cellular and viral promoters, and plays roles in cell cycle progression and cell survival, as well as in cell lineage-specific functions, shown most strikingly to date in hematopoietic lineages [ 9 – 12 ]. TFCP2 is required for Snail1-induced Fibronectin (FN1) expression during EMT [ 13 ]. Yoo et al [ 14 ] documented that TFCP2 overexpression is detected in more than 90% cases of human HCC patients compared to normal liver, and associated with the stage and grade of the disease.…”

Section: Introductionmentioning

confidence: 99%

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Characterization of genome-wide TFCP2 targets in hepatocellular carcinoma: implication of targets FN1 and TJP1 in metastasis

Liu

Zhou

et al. 2015

J Exp Clin Cancer Res

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BackgroundTranscription factor CP2 (TFCP2) is overexpressed in hepatocellular carcinoma(HCC) and correlated with the progression of the disease. Here we report the use of an integrated systems biology approach to identify genome-wide scale map of TFCP2 targets as well as the molecular function and pathways regulated by TFCP2 in HCC.MethodsWe combined Chromatin immunoprecipitation (ChIP) on chip along with gene expression microarrays to study global transcriptional regulation of TFCP2 in HCC. The biological functions, molecular pathways, and networks associated with TFCP2 were identified using computational approaches. Validation of selected target gene expression and direct binding of TFCP2 to promoters were performed by ChIP -PCR and promoter reporter.ResultsTFCP2 fostered a highly aggressive and metastatic phenotype in different HCC cells. Transcriptome analysis showed that alteration of TFCP2 in HCC cells led to change of genes in biological functions involved in cancer, cellular growth and proliferation, angiogenesis, cell movement and attachment. Pathways related to cell movement and cancer progression were also enriched. A quest for TFCP2-regulated factors contributing to metastasis, by integration of transcriptome and ChIP on chip assay, identified fibronectin 1 (FN1) and tight junction protein 1 (TJP1) as targets of TFCP2, and as key mediators of HCC metastasis. Promoter reporter identified the TFCP2-responsive region, and located the motifs of TFCP2-binding sites in the FN1 promoter, which then was confirmed by ChIP-PCR. We further showed that FN1 inhibition blocks the TFCP2-induced increase in HCC cell aggression, and that overexpression of TFCP2 can rescue the effects of FN1 inhibition. Knock down of TJP1 could also rescue, at least in part, the aggressive effect of TFCP2 knockdown in HCC cells.ConclusionsThe identification of global targets, molecular pathways and networks associated with TFCP2, together with the discovery of the effect of TFCP2 on FN1 and TJP1 that are involved in metastasis, adds to our understanding of the mechanisms that determine a highly aggressive and metastatic phenotype in hepatocarcinogenesis.Electronic supplementary materialThe online version of this article (doi:10.1186/s13046-015-0121-1) contains supplementary material, which is available to authorized users.

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Section: Discussionsupporting

confidence: 89%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Characterization of genome-wide TFCP2 targets in hepatocellular carcinoma: implication of targets FN1 and TJP1 in metastasis

Liu

Zhou

et al. 2015

J Exp Clin Cancer Res

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“…In addition, three SNPs (rs35244636, rs116716037, and rs113859079) present in the human WISP1 promoter could alter putative transcription factor binding site, and rs35244636 also could result in the loss of a predicted TFCP2 binding site. Previous studies indicate that TFCP2 can be activated by secreted phosphoprotein 1 (38), activates fibronectin promoter upon epithelial-mesenchymal transition (EMT) induction by snail homolog 1 (Snail1) (39), and enhances angiogenesis by transcriptional activation of matrix metalloproteinase 9 (40) that modulates matrix turnover and inflammation in VILI (41,42). Accordingly, we pursued WISP1 protein in further detail in the current study on VILI in mice.…”

Section: Discussionmentioning

confidence: 99%

WNT1-Inducible Signaling Pathway Protein 1 Contributes to Ventilator-Induced Lung Injury

Li¹,

Liu

et al. 2012

Am J Respir Cell Mol Biol

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Although strides have been made to reduce ventilator-induced lung injury (VILI), critically ill patients can vary in sensitivity to VILI, suggesting gene-environment interactions could contribute to individual susceptibility. This study sought to uncover candidate genes associated with VILI using a genome-wide approach followed by functional analysis of the leading candidate in mice. Alveolar-capillary permeability after high tidal volume (HTV) ventilation was measured in 23 mouse strains, and haplotype association mapping was performed. A locus was identified on chromosome 15 that contained ArfGAP with SH3 domain, ankyrin repeat and PH domain 1 (Asap1), adenylate cyclase 8 (Adcy8), WNT1-inducible signaling pathway protein 1 (Wisp1), and N-myc downstream regulated 1 (Ndrg1). Information from published studies guided initial assessment to Wisp1. After HTV, lung WISP1 protein increased in sensitive A/J mice, but was unchanged in resistant CBA/J mice. Anti-WISP1 antibody decreased HTV-induced alveolar-capillary permeability in sensitive A/J mice, and recombinant WISP1 protein increased HTV-induced alveolar-capillary permeability in resistant CBA/J mice. HTV-induced WISP1 coimmunoprecipitated with glycosylated Toll-like receptor (TLR) 4 in A/J lung homogenates. After HTV, WISP1 increased in strain-matched control lungs, but was unchanged in TLR4 gene-targeted lungs. In peritoneal macrophages from strain-matched mice, WISP1 augmented LPS-induced TNF release that was inhibited in macrophages from TLR4 or CD14 antigen gene-targeted mice, and was attenuated in macrophages from myeloid differentiation primary response gene 88 gene-targeted or TLR adaptor molecule 1 mutant mice. These findings support a role for WISP1 as an endogenous signal that acts through TLR4 signaling to increase alveolar-capillary permeability in VILI.

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“…Third, LSF overexpression can contribute to chemoresistance [ 7 ], since LSF transcriptionally regulates expression of thymidylate synthase [ 10 ], a target of the chemotherapeutic agent 5-fluorouracil [ 7 ]. Finally, nuclear translocation of LSF upon overexpression of Snail can lead to transcriptional upregulation of fibronectin expression, contributing to induction of the epithelial-mesenchymal transition (EMT) [ 11 ].…”

Section: Introductionmentioning

confidence: 99%

Small molecule inhibitors of Late SV40 Factor (LSF) abrogate hepatocellular carcinoma (HCC): Evaluation using an endogenous HCC model

et al. 2015

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TFCP2c/LSF/LBP-1c is required for Snail1-induced fibronectin gene expression

Cited by 19 publications

References 22 publications

Characterization of genome-wide TFCP2 targets in hepatocellular carcinoma: implication of targets FN1 and TJP1 in metastasis

Characterization of genome-wide TFCP2 targets in hepatocellular carcinoma: implication of targets FN1 and TJP1 in metastasis

WNT1-Inducible Signaling Pathway Protein 1 Contributes to Ventilator-Induced Lung Injury

Small molecule inhibitors of Late SV40 Factor (LSF) abrogate hepatocellular carcinoma (HCC): Evaluation using an endogenous HCC model

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