Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0699790 (colon cancer)
 28,837 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Retinol inhibits the growth of all-trans-retinoic acid (ATRA)-resistant human colon cancer cell lines through a retinoic acid receptor (RAR)-independent mechanism. The objectives of the current study were to determine if retinol inhibited the invasion of ATRA-resistant colon cancer cells independent of RAR and the effects of retinol on matrix metalloproteinases (MMPs). Retinol inhibited the migration and invasion of two ATRA-resistant colon cancer cell lines, HCT-116 and SW620, in a dose-dependent manner. To determine if transcription, particularly RAR-mediated transcription, or translation of new genes was required for retinol to inhibit cell invasion, cells were treated with retinol and cycloheximide, actinomycin D, or an RAR pan-antagonist. Treatment of cells with retinol and cycloheximide, actinomycin D, or an RAR pan-antagonist did not block the ability of retinol to inhibit cell invasion. In addition, retinol decreased MMP-1 mRNA levels in both cell lines, MMP-2 mRNA levels in the SW620 cell line, and MMP-7 and -9 mRNA levels in the HCT-116 cell line. Retinol also decreased the activity of MMP-2 and -9 and MMP-9 protein levels while increasing tissue inhibitor of MMP-1 media levels. In conclusion, retinol reduces the metastatic potential of ATRA-resistant colon cancer cells via a novel RAR-independent mechanism that may involve decreased MMP mRNA levels and activity.
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PMID:Retinol inhibits the invasion of retinoic acid-resistant colon cancer cells in vitro and decreases matrix metalloproteinase mRNA, protein, and activity levels. 1751 64

N-Acetylglucosaminyltransferase-V (GnT-V) has been reported to be up-regulated in invasive/metastatic cancer cells, but a comprehensive understanding of how the transferase correlates with the invasive/metastatic potential is not currently available. Through a glycomics approach, we identified 30 proteins, including tissue inhibitor of metalloproteinase-1 (TIMP-1), as a target protein for GnT-V in human colon cancer cell WiDr. TIMP-1 was aberrantly glycosylated as characterized by the addition of beta1,6-N-acetylglucosamine, polylactosaminylation, and sialylation in GnT-V-overexpressing WiDr cells. Compared with normal TIMP-1, the aberrantly glycosylated TIMP-1 showed the weaker inhibition on both matrix metalloproteinase (MMP)-2 and MMP-9, and this aberrancy was closely associated with cancer cell invasion and metastasis in vivo as well as in vitro. Integrated data, both of TIMP-1 expression level and aberrant glycosylation, could provide important information to aid to improve the clinical outcome of colon cancer patients.
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PMID:Functional proteomics study reveals that N-Acetylglucosaminyltransferase V reinforces the invasive/metastatic potential of colon cancer through aberrant glycosylation on tissue inhibitor of metalloproteinase-1. 1787 70

(-)-Epigallocatechin-3-gallate (EGCG), one of the main constituents of green tea, has been reported to function as an antioxidant with chemopreventive potential. In contrast, we have recently reported that EGCG enhanced pro-matrix metalloproteinase (MMP)-7 in HT-29 human colon cancer cells via spontaneous superoxide generation. In the present study, we examined the effects of dietary antioxidants on both spontaneous and EGCG-upregulated proMMP-7 production in HT-29 cells. Benzyl isothiocyanate (BITC), curcumin (CUR), gallic acid (GA), and N-acetyl-L-cysteine (NAC) reduced that production, while each alone did not have any effect on spontaneous production. None of the dietary factors suppressed EGCG-induced hydrogen peroxide generation in the media tested, whereas BITC, GA, and NAC inhibited the EGCG-enhanced activator protein (AP)-1 transcription activity by 126%, 77%, and 97%, respectively. Although CUR abolished the EGCG-upregulated MMP-7 mRNA expression, it unexpectedly enhanced the AP-1 activity by 502%, suggesting that this factor may disrupt the MMP-7 mRNA stabilization process. Together, our results indicate that dietary antioxidants modulate EGCG-induced MMP-7 production through different mechanisms.
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PMID:Modifying effects of dietary factors on (-)-epigallocatechin-3-gallate-induced pro-matrix metalloproteinase-7 production in HT-29 human colorectal cancer cells. 1792 19

Tumor-stromal interaction is implicated in many stages of tumor development, although it remains unclear how genetic lesions in tumor cells affect stromal cells. We have recently shown that inactivation of transforming growth factor-beta family signaling within colon cancer epithelium increases chemokine CC chemokine ligand 9 (CCL9) and promotes recruitment of the matrix metalloproteinase (MMP)-expressing stromal cells that carry CC chemokine receptor 1 (CCR1), the cognate receptor for CCL9. We have further shown that lack of CCR1 prevents the accumulation of MMP-expressing cells at the invasion front and suppresses tumor invasion. These results provide the possibility of a novel therapeutic strategy for advanced cancer--prevention of the recruitment of MMP-expressing cells by chemokine receptor antagonist.
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PMID:Keeping out the bad guys: gateway to cellular target therapy. 1797 48

A thorough understanding of histone acetyltransferase CBP/p300-mediated regulation of gene expression and cell growth is essential to identify mechanisms relevant to the development of histone deacetylase (HDAC) inhibitor-based preventive and therapeutic strategies. We found that knockdown of CBP/p300 interacting coactivator with glutamic acid/aspartic acid-rich tail 2 (CITED2) increased colon cancer cell invasiveness in vitro. Gene expression profiling revealed that CITED2 knockdown induced matrix metalloproteinase-13 (MMP-13) gene expression in colon cancer cells. Butyrate, a naturally occurring HDAC inhibitor, induced CITED2 expression and downregulated MMP-13 expression in RKO cells. Additionally, ectopic expression of CITED2 arrested RKO cell growth. Thus, CITED2 regulates colon cancer invasion and might be a target for HDAC inhibitor-based intervention of colon cancer.
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PMID:A role for CITED2, a CBP/p300 interacting protein, in colon cancer cell invasion. 1805 36

Despite its importance in cell proliferation and tumorigenesis, very little is known about the molecular mechanism underlying the regulation of phospholipase D (PLD) expression. PLD isozymes are significantly co-overexpressed with cancer marker genes in colorectal carcinoma. Phorbol 12-myristate 13-acetate (PMA) treatment, as a mitogenic signal in colon cancer cells, selectively increases PLD1 expression in transcription and post-transcription. Moreover, experiments using intraperitoneal injection of PMA into mice showed selective PLD1 induction in the intestine and lung tissues, which suggests its physiological relevance in vivo. Therefore, we have undertaken a detailed analysis of the effects of PMA on the promoter activity of PLD genes. Protein kinase C inhibitors, but not a protein kinase A inhibitor, were found to suppress the up-regulation of PLD1 but not PLD2. Dominant-negative mutants of Ras, Raf, and MEK suppressed the induction and activity of PLD1. Moreover, depletion of the supposedly involved proteins reduced the endogenous PLD1 protein level. An important role for NFkappaB as a downstream target of ERK in PMA-induced PLD1 induction was also demonstrated using the inhibitor, small interfering RNA, chromatin immunoprecipitation assay, and site-specific mutagenesis. Furthermore, inhibitors of these signaling proteins and depletion of PLD1 suppressed PMA-induced matrix metalloproteinase-9 secretion and PLD1 induction. In conclusion, we demonstrate for the first time that induction of PLD1 through a protein kinase C/Ras/ERK/NFkappaB-dependent pathway is involved in the secretion of matrix metalloproteinase-9 in colorectal cancer cells.
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PMID:Phorbol ester up-regulates phospholipase D1 but not phospholipase D2 expression through a PKC/Ras/ERK/NFkappaB-dependent pathway and enhances matrix metalloproteinase-9 secretion in colon cancer cells. 1808 5

The antimetastatic properties of soybean saponin were investigated by evaluating matrix metalloproteinase (MMP-2 and MMP-9) production in HT-1080 cells. The mRNA expression levels of MMP-2 and MMP-9 were determined by RT-PCR analysis. The levels of secreted MMP-2, MMP-9 and tissue inhibitor of metalloproteinase-2 (TIMP-2) were determined by gelatin zymography and/or ELISA. The invasion of a Matrigel-coated membrane by human fibrosarcoma HT-1080 and HT-29 colon cancer cells was quantitatively assessed by counting the migrated cells. The treatment of HT-1080 cells with soybean saponin inhibited the mRNA expression of and reduced the amounts of secreted MMP-2 and MMP-9, whereas it increased the amount of secreted TIMP-2 dose-dependently. Soybean saponin significantly inhibited the invasion of HT-1080 cells through a Matrigel-coated membrane. The antimetastatic properties by soybean saponin were further confirmed by in vivo mice experiment via the tail vein injection of CT-26 colon cancer cells after feeding the mice the dietary soybean saponin. The incidence of metastatic tumor colonization of lungs of mice moderately decreased 2 weeks after the tail vein injection of CT-26 cells. Our current data support the notion that soybean saponin inhibits tumor cell metastasis by suppressing MMP-2 and MMP-9 productions, and stimulating TIMP-2 secretion, thereby suggesting that soybean saponin has a chemopreventive property against cancer metastasis.
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PMID:Soybean saponin inhibits tumor cell metastasis by modulating expressions of MMP-2, MMP-9 and TIMP- 2. 1808 15

The effect of chitosan oligosaccharide (COS, 1 kDa <MW<3 kDa) on proinflammatory cytokines-induced nitric oxide (NO) production and invasiveness of human colorectal adenocarcinoma HT-29 cells was investigated. COS (0.1-5mg/ ml) suppressed the NO production induced by proinflammatory cytokines (100 U/ml IFN-gamma, 10 ng/ml IL-1alpha, and 25 ng/ml TNF-alpha) in HT-29 cells. Inducible nitric oxide synthase (iNOS) expression induced by these cytokines was inhibited by COS. COS pretreatment inhibited the invasiveness of cytokines-treated HT-29 cells through Matrigel-coated membrane in a dose-dependent manner. COS also inhibited cytokines-induced matrix metalloproteinase (MMP)-2 activity. This study shows that proinflammatory cytokines induce NO production, iNOS expression, and invasiveness of human colorectal adenocarcinoma HT-29 cells. COS pretreatment inhibited cytokines-mediated NO production, iNOS expression, and invasiveness of HT-29 cells. These results provide sufficient information for the further development of COS as an antitumor metastatic agent for the treatment of colon cancer.
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PMID:Inhibition of proinflammatory cytokine-induced invasiveness of HT-29 cells by chitosan oligosaccharide. 1816 53

Tumor cells can stimulate matrix metalloproteinase (MMP) production by stromal cells through cell-cell interactions mediated by cell adhesion molecules such as extracellular matrix metalloproteinase inducer (human CD147/EMMPRIN, mouse CD147/Basigin). This study sought to characterize whether specific tumor-stromal cell interactions mediated by CD147 promote colon cancer growth by utilizing small interfering (si)RNAs directed against human CD147/EMMPRIN or mouse CD147/Basigin in co-cultures of cancer cells with macrophages and fibroblasts and established human SW620 colon cancer xenograft models in immune deficient mice. We show that blockade of host (mouse) CD147/Basigin expression, but not cancer cell-derived CD147/EMMPRIN, suppresses tumor growth in human colon cancer xenografts. Experiments in vitro indicated that colon cancer cell-stromal cell interactions mediated by CD147 lead to increased MMP-2 expression in fibroblasts but not macrophages. Furthermore, expression of host VEGF-A in both fibroblasts and macrophages is independent of CD147 in vitro and in vivo. Interestingly, inhibition of cancer cell-derived EMMPRIN leads to increased MMP-9 levels in vivo. Our findings provide new insights into CD147-mediated tumor-host interactions mediating colon cancer growth.
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PMID:Host CD147 blockade by small interfering RNAs suppresses growth of human colon cancer xenografts. 1850 6

Matrilysin (matrix metalloproteinase-7) plays important roles in tumor progression. It was previously found that matrilysin binds to the surface of colon cancer cells to promote their metastatic potential. In this study, we identified annexin II as a novel membrane-bound substrate of matrilysin. Treatment of human colon cancer cell lines with active matrilysin released a 35 k Da annexin II form, which lacked its N-terminal region, into the culture supernatant. The release of the 35 k Da annexin II by matrilysin was significantly enhanced in the presence of serotonin or heparin. Matrilysin hydrolyzed annexin II at the Lys9-Leu10 bond, thus dividing the protein into an N-terminal nonapeptide and the C-terminal 35 k Da fragment. Annexin II is known to serve as a cell surface receptor for tissue-type plasminogen activator (tPA). Although the matrilysin treatment liberated the 35 k Da fragment of annexin II from the cell surface, it significantly increased tPA binding to the cell membrane. A synthetic N-terminal nonapeptide of annexin II bound to tPA more efficiently than intact annexin II. This peptide formed a heterodimer with intact annexin II in test tubes and on cancer cell surfaces. These and other results suggested that the nonapeptide generated by matrilysin treatment might be anchored to the cell membrane, possibly by binding to intact annexin II, and interact with tPA via its C-terminal lysine. It is supposed that the cleavage of cell surface annexin II by matrilysin contributes to tumor invasion and metastasis by enhancing tPA-mediated pericellular proteolysis by cancer cells.
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PMID:Matrilysin (matrix metalloprotease-7) cleaves membrane-bound annexin II and enhances binding of tissue-type plasminogen activator to cancer cell surfaces. 1872 Nov 40


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