|
Malignant Neoplasms
|
0.100 |
Biomarker
|
group |
BEFREE |
Smad5 homologs Smad2 and DPC4 have recently been linked to human cancer.
|
9264367 |
1997 |
|
Malignant Neoplasms
|
0.100 |
Biomarker
|
group |
BEFREE |
In previous reports, we described that DPC4/Smad4 and Smad2 are mutated in a fraction of human lung cancers and suggested possible roles of the downstream mediators of transforming growth factor-beta (TGF-beta)-elicited signals in the pathogenesis of this most common cancer.
|
9466656 |
1998 |
|
Malignant Neoplasms
|
0.100 |
Biomarker
|
group |
BEFREE |
At least two different Smads, Smad2 and Smad4 (DPC4), have been implicated in human cancer and appear to have tumour-suppressor functions.
|
9862572 |
1998 |
|
Malignant Neoplasms
|
0.100 |
GeneticVariation
|
group |
BEFREE |
However, mechanisms as mutations in TGF-beta receptor II or Smad2 and 4 genes, frequently observed in other human cancers, have only rarely been observed in hepatocellular carcinomas.
|
11170302 |
2001 |
|
Malignant Neoplasms
|
0.100 |
Biomarker
|
group |
BEFREE |
In the present study, we first intended to resolve the role of the hsMAD2 gene in human cancer by determining the potential presence of hsMAD2 mutations in 44 primary bladder tumors, 42 soft-tissue sarcomas and 10 hepatocellular carcinomas.
|
11400114 |
2001 |
|
Malignant Neoplasms
|
0.100 |
AlteredExpression
|
group |
BEFREE |
We also measured the hsMAD2 protein levels in cancer and normal tissues by semi-quantitative immunoblotting.
|
11572763 |
2001 |
|
Malignant Neoplasms
|
0.100 |
Biomarker
|
group |
BEFREE |
We show that interference with endogenous Smad2/3 signaling enhances the malignancy of xenografted tumors of premalignant and well-differentiated tumor cells but strongly suppresses lung metastases of more aggressive carcinoma cells after tail vein injection.
|
14678987 |
2003 |
|
Malignant Neoplasms
|
0.100 |
GeneticVariation
|
group |
BEFREE |
The majority of Smad4 gene mutations in human cancer are missense, nonsense, and frameshift mutations at the mad homology 2 region (MH2), which interfere with the homo-oligomer formation of Smad4 protein and the hetero-oligomer formation between Smad4 and Smad2 proteins, resulting in disruption of TGFbeta signaling.
|
12821112 |
2003 |
|
Malignant Neoplasms
|
0.100 |
AlteredExpression
|
group |
BEFREE |
Smad 2 expression was less in some of the cervical tumor samples than that of nonmalignant samples and six cancer samples showed C-terminal deletions that abolish Smad 2 phosphorylation sites.
|
12894231 |
2003 |
|
Malignant Neoplasms
|
0.100 |
Biomarker
|
group |
BEFREE |
TGF-beta-induced nuclear localization of Smad2 and Smad3 in Smad4 null cancer cell lines.
|
12618756 |
2003 |
|
Malignant Neoplasms
|
0.100 |
AlteredExpression
|
group |
BEFREE |
Our present data based on selective interference with activation of endogenous Smad2 and Smad3 by stable expression of a mutant form of the TGF-beta type I receptor (RImL45) unable to bind Smad2/3 but with a functional kinase again show that reduction in Smad2/3 signaling by expression of RImL45 enhanced the malignancy of xenografted tumors of the well-differentiated MCF10A-derived tumor cell line MCF10CA1h, resulting in formation of larger tumors with a higher proliferative index and more malignant histologic features.
|
15231662 |
2004 |
|
Malignant Neoplasms
|
0.100 |
AlteredExpression
|
group |
BEFREE |
HsMAD2 and BubR1 were significantly higher in cancer tissue than in adjacent normal tissue (P < 0.01).
|
18691855 |
2008 |
|
Malignant Neoplasms
|
0.100 |
Biomarker
|
group |
BEFREE |
At the molecular level, RBBP9 activity overcomes TGF-beta-mediated antiproliferative signaling by reducing Smad2/3 phosphorylation, a previously unknown role for a serine hydrolase in cancer biology.
|
20080647 |
2010 |
|
Malignant Neoplasms
|
0.100 |
AlteredExpression
|
group |
BEFREE |
This process includes the induction of Smad2/3 phosphorylation, the increase of Smad2/3 transcriptional activity and the upregulation of the expression of target genes involved in EMT and cancer progression (such as TGF-β1, MMP-2, MMP-9, plasminogen activator inhibitor type-1, vascular endothelial growth factor, Snail and Slug), thus promoting cancer cell mobility and invasion.
|
21441952 |
2011 |
|
Malignant Neoplasms
|
0.100 |
Biomarker
|
group |
BEFREE |
CNVs of Smad2 showed statistical differences between cancer samples (both SCC and BCC) and normal tissues (p<0.05).
|
22301403 |
2012 |
|
Malignant Neoplasms
|
0.100 |
AlteredExpression
|
group |
BEFREE |
Real time PCR was used to measure mRNA expression of Smad2 and Smad3 in cancer and surrounding non-tumor tissue.
|
22539990 |
2012 |
|
Malignant Neoplasms
|
0.100 |
AlteredExpression
|
group |
BEFREE |
Gene expression profiles from cDNA microarray analyses of the same stromal tissue samples revealed that putative targets of these miRNA clusters, predicted by Target Scan, such as TGFBR2, SMAD2, and BMP family genes, were significantly downregulated in cancer stromal tissue.
|
22452939 |
2012 |
|
Malignant Neoplasms
|
0.100 |
AlteredExpression
|
group |
BEFREE |
By contrast, SMAD2 expression was upregulated in most malignant tumors.
|
23866946 |
2013 |
|
Malignant Neoplasms
|
0.100 |
AlteredExpression
|
group |
BEFREE |
External validation by mRNA expression showed a good agreement between hypermethylation in cancer and down-regulated mRNA expression of the genes EDNRB1, GPC6 and SMAD2, and between hypomethylation and up-regulated mRNA expression of the CASP8 and DCLRE1C genes.
|
24811787 |
2014 |
|
Malignant Neoplasms
|
0.100 |
AlteredExpression
|
group |
BEFREE |
SGPP1 and Smad2 at mRNA and protein levels were negatively correlated with miR-27a in human colorectal cancer tissues and cancer cell lines.
|
25166914 |
2014 |
|
Malignant Neoplasms
|
0.100 |
AlteredExpression
|
group |
BEFREE |
Verified by literature and public database, the pathway TGFβ1-TGFβR1-SMAD2/3-SMAD4/AR-OCIAD2 was detected, which concealed the androgen receptor (AR) which was the possible transcription factor of OCIAD2 in TGFβsignal, and it well explained the mechanism of TGFβ induced OCIAD2 expression in cancer microenvironment, therefore providing an important clue for the future functional analysis of OCIAD2 in tumor pathogenesis.
|
24949437 |
2014 |
|
Malignant Neoplasms
|
0.100 |
GeneticVariation
|
group |
BEFREE |
Furthermore, the analysis of the Cancer Genome Atlas data revealed that in CRC without microsatellite instability, overexpression of Myc and inactivation of Smads (including acquired mutations in SMAD2) are mutually exclusive, with odds ratio less than 0.1.
|
24627270 |
2014 |
|
Malignant Neoplasms
|
0.100 |
Biomarker
|
group |
BEFREE |
Smad2 is a key element downstream of the TGF-β signaling pathway to regulate cancer metastasis by promoting epithelial to mesenchymal transition and maintaining the cancer stem cell (CSC) phenotype.
|
25980495 |
2015 |
|
Malignant Neoplasms
|
0.100 |
Biomarker
|
group |
BEFREE |
We previously reported that aberrant TGF-β/Smad2/3 signaling in endometrial cancer (ECA) leads to continuous ubiquitylation of p27(kip1)(p27) by the E3 ligase SCF-Skp2/Cks1 causing its degradation, as a putative mechanism involved in the pathogenesis of this cancer.
|
26963853 |
2016 |
|
Malignant Neoplasms
|
0.100 |
Biomarker
|
group |
BEFREE |
Here we investigated the role of DLX2 in association with radiation-induced epithelial to mesenchymal transition (EMT) and stem cell-like properties and its regulation by Smad2/3 signaling in irradiated A549 and MDA-MB-231 human cancer cell lines.
|
26799321 |
2016 |