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)

We have compared the intracellular localization of plasma membrane proteins anchored either with a transmembrane segment or with a glycosylphosphatidylinositol moiety to estimate the effects of membrane anchor on protein segregation in the non-polarized form of the human colon cancer cell line HT-29 18. We have monitored two endogenous proteins: the carcinoembryonic antigen, a glycosylphosphatidylinositol protein and the transmembrane protein dipeptidyl peptidase IV, and two transfected proteins: the glycosylphosphatidylinositol protein Thy-1 and an engineered transmembrane form of Thy-1. Using immunocytochemistry on ultra-thin cryosections and confocal microscopy, we detected a carcinoembryonic antigen-rich vesicular compartment, excluding classical pre-lysosomal and lysosomal markers such as mannose 6-phosphate receptor, lamp-1 and cathepsin D. This compartment, where carcinoembryonic antigen accumulated, excluded the transmembrane protein dipeptidyl peptidase IV and was reduced during the polarization of the cells. Moreover, the glycosylphosphatidylinositol form of Thy-1 also accumulated in the carcinoembryonic antigen-rich compartment whereas the transmembrane form of Thy-1 was excluded. We proposed that, in the non-polarized HT-29 18 cells, accumulation of glycosylphosphatidylinositol proteins independently of transmembrane proteins reveals different intracellular fates for proteins according to their anchor in the plasma membrane.
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PMID:GPI membrane anchor is determinant in intracellular accumulation of apical plasma membrane proteins in the non-polarized human colon cancer cell line HT-29 18. 787 37

Fas ligand is a type II transmembrane protein which can induce apoptosis in Fas-expressing cells. Recent reports indicate that expression of FasL in transplanted cells may cause graft rejection and, on the other hand, tumor cells may lose their tumorigenicity when they are engineered to express FasL. These effects could be related to recruitment of neutrophils by FasL with activation of their cytotoxic machinery. In this study we investigated the antitumor effect of allogenic fibroblasts engineered to express FasL. Fibroblasts engineered to express FasL (PA317/FasL) did not exert toxic effects on transformed liver cell line (BNL) or colon cancer cell line (CT26) in vitro, but they could abrogate their tumorigenicity in vivo. Histological examination of the site of implantation of BNL cells mixed with PA317/FasL revealed massive infiltration of polymorphonuclear neutrophils and mononuclear cells. A specific immune protective effect was observed in animals primed with a mixture of BNL or CT26 and PA317/FasL cells. Rechallenge with tumor cells 14 or 100 days after priming resulted in protection of 100 or 50% of animals, respectively. This protective effect was due to CD8+ cells since depletion of CD8+ led to tumor formation. In addition, treatment of pre-established BNL tumors with a subcutaneous injection of BNL and PA317/FasL cell mixture at a distant site caused significant inhibition of tumor growth. These data demonstrate that allogenic cells engineered with FasL are able to abolish tumor growth and induce specific protective immunity when they are mixed with neoplastic cells.
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PMID:Antitumor effect of allogenic fibroblasts engineered to express Fas ligand (FasL). 1002 41

The DCC (deleted in colon cancer) gene has a brain restricted high expression pattern. It encodes a transmembrane protein of the immunoglobulin superfamily identified as the netrin-1 receptor. It might be a member of the so called "brain-lymphoid" molecules, which control key cell surface events. To test this hypothesis we have assessed the DCC mRNA level in human normal and malignant myeloid and lymphoid cells. A high mRNA content has been observed only in mature B cells at the secreting or presecreting stage. Expression of DCC was also assessed in the anti-CD40 model of immunopoiesis. Activation of purified tonsillar B cells by anti-CD 40 antibody strongly increased the DCC mRNA level and this effect was dramatically enhanced by the association of IL-2 + IL-10, which is a potent and selective in vitro inducer of the B cell memory phenotype. In contrast no effect has been detected after activation of T cells by anti-CD3. These data suggest that the DCC encoded netrin receptor is involved in B cell immunopoiesis.
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PMID:Upregulation of the netrin receptor (DCC) gene during activation of b lymphocytes and modulation by interleukins. 1135 76

Efforts are increasing to identify and evaluate diagnostic and therapeutic markers for prostate cancer patients. One of these, prostate-specific membrane antigen (PSMA), a transmembrane protein highly expressed in all types of prostatic tissue (eg, benign epithelium, benign prostatic hyperplasia, prostatic intra-epithelial neoplasia and adenocarcinomas, with increased binding affinity for malignant cells), is becoming an increasingly important diagnostic and therapeutic marker, not only for prostate cancer, but possibly for other malignant lesions. Recent studies have demonstrated PSMA expression in endothelial cells of tumor-associated neovasculature (including carcinoma of the colon, breast, bladder, pancreas, kidney and melanoma), thus greatly expanding its possible beneficial role, especially as new anti-PSMA mAbs continue to be developed and refined. Future diagnostic and therapeutic interventions utilizing these antibodies will become increasingly important in not only prostate cancer but perhaps many other different malignancy types.
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PMID:Monoclonal antibodies and prostate-specific membrane antigen. 1524 49

The Hedgehog (Hh) signalling pathway is crucial for normal development and patterning of numerous human organs including the gut. Hh proteins are also expressed during gastric gland development and gastric epithelial differentiation in adults. Recently, dysregulation of these developmentally important genes has been implicated in cancer, leading to the present study of the expression of Hh signalling proteins in colon cancer. In this study, normal colon and colonic lesions (hyperplastic polyp, adenoma, and colonic adenocarcinoma) were examined by immunohistochemistry using antibodies against Hh signalling molecules: the secreted protein Sonic hedgehog (SHH), its receptor Patched (PTCH), and the PTCH-associated transmembrane protein Smoothened (SMOH). The study shows that Hh signalling pathway members are expressed in normal colonic epithelium. SHH was expressed at the top of the crypts and in a few basally located cells, while PTCH was detected in the neuroendocrine cells and SMOH at the brush border of superficial epithelium. RT-PCR analysis of laser-microdissected crypts from normal human colon confirmed that mRNAs encoding these proteins were expressed in colonic epithelium. Expression of SHH, PTCH, and SMOH was up-regulated in hyperplastic polyps, adenomas, and adenocarcinomas of the colon, and SHH expression correlated with increased expression of the proliferation marker Ki-67 in all lesions examined. To address whether the Hh signalling pathway is functional in the gut, the effect of Shh on epithelial cells in vitro was explored by treating primary murine colonocytes with either Shh peptide or neutralizing anti-Shh antibody. The proportion of cells in the S-phase was assessed by bromodeoxyuridine (BrdU) incorporation. It was found that exogenous Shh promotes cell proliferation in colonocytes, while anti-Shh inhibits proliferation, suggesting that Shh is required during proliferation of epithelial cells in vitro. It is suggested that SHH is required during epithelial proliferation in the colon and that there is a possible role for Hh signalling in epithelial colon tumour progression in vivo.
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PMID:Expression of Sonic hedgehog pathway genes is altered in colonic neoplasia. 1525 93

Tissue factor (TF) initiates the coagulation cascade but also plays a role in cancer and metastasis. This transmembrane protein is frequently upregulated on tumor cells and cells that show metastatic behavior. Furthermore, it is a significant risk factor for hepatic metastasis in patients suffering from colon cancer. Recently, it has been shown that TF, together with its natural ligand factor VIIa, induces intracellular changes, such as signal transduction cascades, gene transcription, and protein synthesis. Moreover, TF:factor VIIa interaction leads to survival of cells that have been stimulated to undergo apoptosis. Together with TF-dependent processes such as angiogenesis, these intracellular phenomena form a plausible explanation for the influence of TF on metastasis. In this review, we will discuss these phenomena in more detail and hypothesize on their role in TF-driven metastasis.
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PMID:Tissue factor and cancer metastasis: the role of intracellular and extracellular signaling pathways. 1550 77

The role of promoter methylation in the process of cancer cell metastasis has, however, not yet been studied. Recently, methylation of the TPEF (transmembrane protein containing epidermal growth factor and follistatin domain) gene was reported in human colon, gastric, and bladder cancer cells. Using the Methylight assay, TPEF/HPP1 gene methylation was assessed in primary colorectal cancers (n = 47), matched normal colon mucosa, as well as in the liver metastasis of 24 patients with colorectal cancer, and compared to the methylation status of the TIMP-3, APC, DAPK, caveolin-2, and p16 genes. TPEF was frequently methylated in primary colorectal cancers (36 of 47) compared to the normal colon mucosa (1 of 21) (P < .0001), and TPEF mRNA expression in colon cancer cell lines was restored after treatment with 5-aza-2'-deoxycytidine. The p16 and APC genes were also frequently methylated in primary colorectal cancers (P < .02) compared to the normal colon mucosa. Interestingly, promoter methylation was significantly more frequent in proximal, nonrectal cancers (P < .05). Furthermore, a high degree of methylation of the TPEF gene was also observed in liver metastasis (19 of 24). In summary, we observed frequent TPEF methylation in primary colorectal cancers and liver metastases, indicating that epigenetic alterations are not only present in the early phases of carcinogenesis, but are also common in metastatic lesions. The high frequency of TPEF methylation in this series of colorectal cancers underscores the importance of epigenetic changes as targets for the development of molecular tests for cancer diagnosis.
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PMID:Hypermethylation of the TPEF/HPP1 gene in primary and metastatic colorectal cancers. 1620 79

Transmembrane proteins with extracellular Frizzled domain, such as ROR1, ROR2, MUSK, MFRP, FZD1, FZD2, FZD3, FZD4, FZD5, FZD6, FZD7, FZD8, FZD9 and FZD10, are key molecules for WNT signaling network. Here, comparative integromics analyses on ROR1 and ROR2 orthologs were performed by using bioinformatics. Zebrafish ror2 gene, consisting of nine exons, was identified within CR-450684.3 genome sequence. CV490605.1 EST corresponded to the 5'-end of zebrafish ror2 mRNA, and BM533602.1 EST corresponded to the 3'-end. Zebrafish ror2 gene was found to encode a 939-aa transmembrane protein, showing 71.7% and 56.2% total amino-acid identity with human ROR2 and ROR1, respectively. Immunoglobulin-like domain, Frizzled domain, Kringle domain within the extracellular region, tyrosine kinase domain, Ror homology C-terminal (RORHC) domain and juxta-C-terminal LLGD motif within the cytoplasmic region were conserved among vertebrate ROR1 and ROR2 orthologs. SH2 binding site within the RORHC domain was conserved among vertebrate ROR2 orthologs, but not among vertebrate ROR1 orthologs. ROR1 mRNA was expressed in embryonic stem (ES) cells, infant brain, renal cancer, and colon cancer. ROR2 mRNA was expressed in parathyroid, testis, uterus, and also in diffuse type gastric cancer with signet ring cell features. ROR2 promoter rather than ROR1 promoter was more evolutionarily conserved. WNT5A and ROR family receptors, co-expressed in ES cells and gastric cancer, are implicated in the planar cell polarity (PCP) pathway. ROR1 and ROR2 are the pharmacogenomics targets in the fields of stem cell biology and oncology.
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PMID:Comparative genomics on ROR1 and ROR2 orthologs. 1621 13

The transmembrane protein-tyrosine phosphatase (PTP) DEP-1 (density-enhanced phosphatase) is a candidate tumor suppressor in the colon epithelium. We have explored the function of DEP-1 in colon epithelial cells by inducible re-expression in a DEP-1-deficient human colon cancer cell line. Density-enhanced phosphatase-1 re-expression led to profound inhibition of cell proliferation and cell migration, and was associated with cytoskeletal rearrangements. These effects were dependent on the PTP activity of DEP-1 as they were not observed with cells expressing the catalytically inactive DEP-1 C1239S variant. shRNA-mediated suppression of DEP-1 in a colon epithelial cell line with high endogenous DEP-1 levels enhanced proliferation, further supporting the antiproliferative function of DEP-1. Nutrients, which are considered to be chemoprotective with respect to colon cancer development, including butyrate, green tea and apple polyphenols, had the capacity to elevate transcription of endogenous DEP-1 mRNA and expression of DEP-1 protein. Upregulation of DEP-1 expression, and in turn inhibition of cell growth and migration may present a previously unrecognized mechanism of chemoprevention by nutrients.
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PMID:DEP-1 protein tyrosine phosphatase inhibits proliferation and migration of colon carcinoma cells and is upregulated by protective nutrients. 1668 45

CD147 is a multifunctional transmembrane protein and promotes cancer progression. We found that the anti-human CD147 mouse monoclonal antibody MEM-M6/1 strongly induces necrosis-like cell death in LoVo, HT-29, WiDr, and SW620 colon cancer cells and A2058 melanoma cells, but not in WI-38 and TIG-113 normal fibroblasts. Silencing or overexpression of CD147 in LoVo cells enhanced or decreased the MEM-M6/1 induced cell death, respectively. CD147 is known to form complex with proton-linked monocarboxylate transporters (MCTs), which is critical for lactate transport and intracellular pH (pHi) homeostasis. In LoVo cells, CD147 and MCT-1 co-localized on the cell surface, and MEM-M6/1 inhibited the association of these molecules. MEM-M6/1 inhibited lactate uptake, lactate release, and reduced pHi. Further, the induction of acidification was parallel to the decrease of the glycolytic flux and intracellular ATP levels. These effects were not found in the normal fibroblasts. As cancer cells depend on glycolysis for their energy production, CD147 inhibition might induce cell death specific to cancer cells.
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PMID:Blocking CD147 induces cell death in cancer cells through impairment of glycolytic energy metabolism. 1861 31


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