Identification and characterization of the hypoxia-responsive element in human stanniocalcin-1 gene

Law, Alice Y.S.; Ching, L.Y.; Lai, Keng Po; Wong, Chris K C

doi:10.1016/j.mce.2009.07.007

Cited by 45 publications

(46 citation statements)

References 63 publications

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“…These future analyses should also consider recent studies, which have implicated STC1, in noncancer models, as a regulator of inflammation, macrophage mobility, and vascular permeability (39)(40)(41)(42). Interestingly, earlier studies have also shown that hypoxia, a prometastatic stimuli, also leads to the upregulation of STC1 (43).…”

Section: Discussionmentioning

confidence: 88%

STC1 Expression By Cancer-Associated Fibroblasts Drives Metastasis of Colorectal Cancer

et al. 2013

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Platelet-derived growth factor (PDGF) receptor signaling is a major functional determinant of cancerassociated fibroblasts (CAF). Elevated expression of PDGF receptors on stromal CAFs is associated with metastasis and poor prognosis, but mechanism(s) that underlie these connections are not understood. Here, we report the identification of the secreted glycoprotein stanniocalcin-1 (STC1) as a mediator of metastasis by PDGF receptor function in the setting of colorectal cancer. PDGF-stimulated fibroblasts increased migration and invasion of cocultured colorectal cancer cells in an STC1-dependent manner. Analyses of human colorectal cancers revealed significant associations between stromal PDGF receptor and STC1 expression. In an orthotopic mouse model of colorectal cancer, tumors formed in the presence of STC1-deficient fibroblasts displayed reduced intravasation of tumor cells along with fewer and smaller distant metastases formed. Our results reveal a mechanistic basis for understanding the contribution of PDGF-activated CAFs to cancer metastasis. Cancer Res; 73(4);

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Section: Discussionmentioning

confidence: 88%

STC1 Expression By Cancer-Associated Fibroblasts Drives Metastasis of Colorectal Cancer

et al. 2013

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“…As a result of cell concentrations and nutrient availability, MSCs in scaffolds proliferated into the pores supported by an ECM composed mostly of GAGs. Despite the low amounts of measured GAGs compared to pellet cultures of MSCs [40], histological analysis for GAGs showed that stromal cells adhesion into the center of the pore was morphologically supported by a loosely associated ECM with nodules of stromal cells organized into circular patterns. This organization occurred in all axis of the interconnected pore network with an ECM that had similar structural characteristics to those observed during mesenchymal morphogenesis [18].…”

Section: Discussionmentioning

confidence: 89%

Spatiotemporal proliferation of human stromal cells adjusts to nutrient availability and leads to stanniocalcin-1 expression in vitro and in vivo

et al. 2015

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Cells and tissues are intrinsically adapted to molecular gradients and use them to maintain or change their activity. The effect of such gradients is particularly important for cell populations that have an intrinsic capacity to differentiate into multiple cell lineages, such as bone marrow derived mesenchymal stromal cells (MSCs). Our results showed that nutrient gradients prompt the spatiotemporal organization of MSCs in 3D culture. Cells adapted to their 3D environment without significant cell death or cell differentiation. Kinetics data and whole-genome gene expression analysis suggest that a low proliferation activity phenotype predominates in stromal cells cultured in 3D, likely due to increasing nutrient limitation. These differences implied that despite similar surface areas available for cell attachment, higher cell concentrations in 3D reduced MSCs proliferation, while activating hypoxia related-pathways. To further understand the in vivo effects of both proliferation and cell concentrations, we increased cell concentrations in small (1.8 μl) implantable wells. We found that MSCs accumulation and conditioning by nutrient competition in small volumes leads to an ideal threshold of cell-concentration for the induction of blood vessel formation, possibly signaled by the hypoxia-related stanniocalcin-1 gene.

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“…Our previous studies have revealed that, STC1 is a HIF-1 target gene and was epigenetic regulated by histone deacetylation [Yeung et al, 2005;Law et al, 2008Law et al, , 2010. The induction of STC1 expression was shown to be regulated by p53 and NFkB signaling [Lai et al, 2007;Law et al, 2008].…”

Section: Discussionmentioning

confidence: 98%

“…Intriguingly the 5 0 -untranslated region of STC1 gene showed long stretches of CAG trinucleotide repeats, which may also relate to genetic instability and transcriptional silencing [Chang et al, 1998;Varghese et al, 1998;Parniewski and Staczek, 2002]. Our previous and other studies have revealed that, STC1 is a hypoxia-inducible factor-1 (HIF-1) target gene [Eisenhofer et al, 2004;Yeung et al, 2005; Westberg et al, 2007a,b;Law et al, 2010], probably expressed in tumor microenvironment and was involved in the process of apoptosis [Zhang et al, 2000;Wu et al, 2006;Lai et al, 2007;Law et al, 2008;Block et al, 2009;Nguyen et al, 2009] and cell proliferation [Daniel and Lange, 2009]. The transcriptional factor specificity protein 1 (Sp1) is known to be important in the transcriptional regulation of genes involved in cancer cell growth, differentiation, and apoptosis [Black et al, 2001;Deniaud et al, 2006Deniaud et al, , 2009.…”

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confidence: 94%

Sp1 is a transcription repressor to stanniocalcin-1 expression in TSA-treated human colon cancer cells, HT29

et al. 2011

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Our previous study demonstrated that, stanniocalcin-1 (STC1) was a target of histone deacetylase (HDAC) inhibitors and was involved in trichostatin A (TSA) induced apoptosis in the human colon cancer cells, HT29. In this study, we reported that the transcriptional factor, specificity protein 1 (Sp1) in association with retinoblastoma (Rb) repressed STC1 gene transcription in TSA-treated HT29 cells. Our data demonstrated that, a co-treatment of the cells with TSA and Sp1 inhibitor, mithramycin A (MTM) led to a marked synergistic induction of STC1 transcript levels, STC1 promoter (1 kb)-driven luciferase activity and an increase of apoptotic cell population. The knockdown of Sp1 gene expression in TSA treated cells, revealed the repressor role of Sp1 in STC1 transcription. Using a protein phosphatase inhibitor okadaic acid (OKA), an increase of Sp1 hyperphosphorylation and so a reduction of its transcriptional activity, led to a significant induction of STC1 gene expression. Chromatin immunoprecipitation (ChIP) assay revealed that Sp1 binding on STC1 proximal promoter in TSA treated cells. The binding of Sp1 to STC1 promoter was abolished by the co-treatment of MTM or OKA in TSA-treated cells. Re-ChIP assay illustrated that Sp1-mediated inhibition of STC1 transcription was associated with the recruitment of another repressor molecule, Rb. Collectively our findings identify STC1 is a downstream target of Sp1.

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Identification and characterization of the hypoxia-responsive element in human stanniocalcin-1 gene

Cited by 45 publications

References 63 publications

STC1 Expression By Cancer-Associated Fibroblasts Drives Metastasis of Colorectal Cancer

STC1 Expression By Cancer-Associated Fibroblasts Drives Metastasis of Colorectal Cancer

Spatiotemporal proliferation of human stromal cells adjusts to nutrient availability and leads to stanniocalcin-1 expression in vitro and in vivo

Sp1 is a transcription repressor to stanniocalcin-1 expression in TSA-treated human colon cancer cells, HT29

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