Differential Binding of the Transcription Factors Sp1, AP-1, and NFI to the Promoter of the Human α5 Integrin Gene Dictates Its Transcriptional Activity

Gingras, Marie-Ève; Masson-Gadais, Bénédicte; Zaniolo, Karine; Leclerc, Suzanne; Drouin, Régen; Germain, Lucie; Guérin, Sylvain L.

doi:10.1167/iovs.08-2059

Cited by 27 publications

(39 citation statements)

References 50 publications

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“…At the underlying molecular level, there is accumulating evidence that indicates that the promoter activity of integrin a5 can be transactivated by transcriptional factors such as activator protein 1 (AP-1; refs. 40, 41), SP-1 (40,41), and CCAAT/enhancer binding proteins (C/EBP; refs. 40,42).…”

Section: Discussionmentioning

confidence: 99%

Connective Tissue Growth Factor Acts as a Therapeutic Agent and Predictor for Peritoneal Carcinomatosis of Colorectal Cancer

Lin

Chang

Chen

et al. 2011

Clinical Cancer Research

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Purpose: Here, we aimed to investigate the role of connective tissue growth factor (CTGF) in peritoneal carcinomatosis (PC) associated with colorectal cancer (CRC) and to characterize the underlying mechanism of CTGF mediating adhesion.Experimental Design: A cohort of 136 CRC patient specimens was analyzed in this study. CRC cell lines were used for in vitro adhesion assay and in vivo peritoneal dissemination experiment. Recombinant CTGF protein treatment, transfection of CTGF expression plasmids, and knockdown of CTGF expression in CRC cells were utilized to evaluate the integrin a5, which served as a target of CTGF in inhibiting peritoneal seeding.Results: The analysis of CRC tissues revealed an inverse correlation between CTGF expression and prevalence of PC. Lower CTGF level in CRC patients was associated with higher peritoneal recurrence rate after surgery. Inducing CTGF expression in cancer cells resulted in decreased incidence of PC and increased rate of mice survival. The mice received intraperitoneal injection of recombinant CTGF protein simultaneously with cancer cells or following tumor formation; in both cases, peritoneal tumor dissemination was found to be effectively inhibited in the mouse model. Functional assay revealed that CTGF significantly decreased the CRC cell adhesion ability, and integrin a5 was confirmed by reverse transcriptase PCR and functional blocking assay as a downstream effector in the CTGF-mediated inhibition of CRC cell adhesion.Conclusions: CTGF acts as a molecular predictor of PC and could be a potential therapeutic target for the chemoprevention and treatment of PC in CRC patients.

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Section: Discussionmentioning

confidence: 99%

Connective Tissue Growth Factor Acts as a Therapeutic Agent and Predictor for Peritoneal Carcinomatosis of Colorectal Cancer

Lin

Chang

Chen

et al. 2011

Clinical Cancer Research

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“…FN and its canonical α5β1 integrin receptors activate transcriptional responses linked to the AP-1 complex (42). Interestingly, the AP-1 response element was also identified in the α5 promoter (43). Recent studies indicate that the PI3K/Akt and mToR pathways control the expression of FN (44).…”

Section: Discussionmentioning

confidence: 99%

Priming and potentiation of DNA damage response by fibronectin in human colon cancer cells and tumor-derived myofibroblasts

et al. 2011

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We have previously shown that the genotoxin-induced apoptosis in mouse embryo fibroblasts was enhanced by the extracellular matrix protein fibronectin (FN). In the present study, we tested the hypothesis that FN regulates the DNA damage response (DDR) signaling pathways in HCT116 (p53-wt) and HT29 (p53-mut) human colon cancer cells and tumor-derived myofibroblasts. DNA damage recognition mechanisms were analyzed by immunofluorescence staining, cell cycle analysis and immunoblotting addressed at specific molecular sensors and executors involved in the DDR pathways. The results show that FN, but not collagen type IV or Matrigel, initiates and potentiates the DDR to the anticancer drug cisplatin in an α5 integrin and cell cycle-dependent manner (S and G2/M phases) in human colon cancer cells. Accordingly, we demonstrate that adhesion of HCT116 cells to FN upregulated the expression of α5 integrin FN receptors at the cell surface. These FN-induced DDR pathways include the concerted phosphorylation of histone H2AX on Ser139 detected as nuclear foci (γ-H2AX, 15 and 25 kDa forms), of ataxia telangiectasia mutated (ATM-Ser1981), checkpoint kinase 2 (CHK2-Thr68, 62 and 67 kDa) and p53-Ser15. These FN-induced γ-H2AX signals were interrupted or attenuated by selective inhibitors acting on the DDR pathway kinases, including wortmannin (targeting the phosphatidylinositol-3-kinase-related protein kinases, PIKK), KU55933 (ATM), NU7026 (DNA-dependent protein kinase catalytic subunit, DNA-PK-cs) and SP600125 (JNK2, stress activated protein kinase/c-Jun N-terminal kinase-2). Adhesion to FN also potentiated the γ-H2AX signals and the cytotoxic effects of cisplatin in human colon tumor-derived myofibroblasts. These data provide evidence that FN promotes DNA damage recognition and chemosensitization to cisplatin via the potentiation of the DNA damage signaling responses in human colon cancer cells and tumor-derived myofibroblasts.

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“…1 and 1 . 0 mM) for 2 or 24 h, Compound C (20 and 40 mM) for 2 or 24 h, and mithramycin A (100 and 200 nM) for 24 h. Mouse gAd (Gingras et al 2009) was purchased from R&D systems (Minneapolis, MN, USA), AICAR and Compound C from Sigma, and mithramycin A from AppliChem (Ottoweg, Darmstadt, Germany).…”

Section: Culture Of Neuronsmentioning

confidence: 99%

Adiponectin inhibits KISS1 gene transcription through AMPK and specificity protein-1 in the hypothalamic GT1-7 neurons

Wen

Liu²,

Bi³

et al. 2012

Journal of Endocrinology

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Adiponectin secreted from adipose tissues plays a role in the regulation of energy homeostasis, food intake, and reproduction in the hypothalamus. We have previously demonstrated that adiponectin significantly inhibited GNRH secretion from GT1-7 hypothalamic GNRH neuron cells. In this study, we further investigated the effect of adiponectin on hypothalamic KISS1 gene transcription, which is the upstream signal of GNRH. We found that globular adiponectin (gAd) or AICAR, an artificial AMPK activator, decreased KISS1 mRNA transcription and promoter activity. Conversely, inhibition of AMPK by Compound C or AMPKa1-SiRNA augmented KISS1 mRNA transcription and promoter activity. Additionally, gAd and AICAR decreased the translocation of specificity protein-1 (SP1) from cytoplasm to nucleus; however, Compound C and AMPKa1-siRNA played an inverse role. Our experiments in vivo demonstrated that the expression of Kiss1 mRNA was stimulated twofold in the Compound C-treated rats and decreased about 60-70% in gAd-or AICAR-treated rats compared with control group. The numbers of kisspeptin immunopositive neurons in the arcuate nucleus region of Sprague Dawley rats mimicked the same trend seen in Kiss1 mRNA levels in animal groups with different treatments. In conclusion, our results provide the first evidence that adiponectin reduces Kiss1 gene transcription in GT1-7 cells through activation of AMPK and subsequently decreased translocation of SP1.

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Differential Binding of the Transcription Factors Sp1, AP-1, and NFI to the Promoter of the Human α5 Integrin Gene Dictates Its Transcriptional Activity

Abstract: These results suggest that alpha5 gene expression is likely dictated by subtle alterations in the nuclear ratio of TFs that either repress (NFI) or activate (Sp1 and AP-1) alpha5 transcription in corneal epithelial cells.

Cited by 27 publications

References 50 publications

Connective Tissue Growth Factor Acts as a Therapeutic Agent and Predictor for Peritoneal Carcinomatosis of Colorectal Cancer

Connective Tissue Growth Factor Acts as a Therapeutic Agent and Predictor for Peritoneal Carcinomatosis of Colorectal Cancer

Priming and potentiation of DNA damage response by fibronectin in human colon cancer cells and tumor-derived myofibroblasts

Adiponectin inhibits KISS1 gene transcription through AMPK and specificity protein-1 in the hypothalamic GT1-7 neurons

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