Carcinogenesis
|
0.100 |
GeneticVariation
|
phenotype |
BEFREE |
Therefore, we propose that loss of CTCF-dependent imprinting of tumor-promoting genes, such as IGF2 and TERT, results from a defective TGF-β pathway and is responsible at least in part for BWS-associated tumorigenesis as well as sporadic human cancers that are frequently associated with SPTBN1 and SMAD3 mutations.
|
26784546 |
2016 |
Carcinogenesis
|
0.100 |
GeneticVariation
|
phenotype |
BEFREE |
Colorectal cancers (CRCs) frequently harbor somatic mutations in the pathway members TGFBR2 and SMAD4, but to what extent mutations in SMAD2 or SMAD3 contribute to tumorigenesis is unclear.
|
23139211 |
2013 |
Carcinogenesis
|
0.100 |
GeneticVariation
|
phenotype |
BEFREE |
This study shows that inactivating germline alterations in SMAD3 and SMAD4 are rare, suggesting a limited role in driving tumorigenesis.
|
21835029 |
2011 |
Carcinogenesis
|
0.100 |
Biomarker
|
phenotype |
BEFREE |
Characterization of dextran sodium sulfate-induced inflammation and colonic tumorigenesis in Smad3(-/-) mice with dysregulated TGFβ.
|
24244446 |
2013 |
Carcinogenesis
|
0.100 |
Biomarker
|
phenotype |
BEFREE |
To understand how SKI promotes tumor growth we used gain- and loss-of-function approaches and found that simultaneously to blocking the TGF-beta-growth inhibitory pathway, SKI promotes the switch of Smad3 from tumor suppression to oncogenesis by favoring phosphorylations of the Smad3 linker region in melanoma cells but not in normal human melanocytes.
|
19845874 |
2009 |
Carcinogenesis
|
0.100 |
Biomarker
|
phenotype |
BEFREE |
These findings suggest that the Smad3 gene may not play an important role in the tumorigenesis of colorectal cancers.
|
9464505 |
1998 |
Carcinogenesis
|
0.100 |
Biomarker
|
phenotype |
BEFREE |
After undergoing successful antiviral therapy, patients with chronic hepatitis C could experience a lower risk of HCC as Smad3 phospho-isoform signaling reverses from potential carcinogenesis to tumor suppression.
|
25253939 |
2014 |
Carcinogenesis
|
0.100 |
Biomarker
|
phenotype |
BEFREE |
Although genetic mutation of Smad3 has not been reported, CDK phosphorylation of Smad3 may provide an epigenetic mechanism for inhibition of the tumor suppressive function of Smad3 during the early stages of tumorigenesis.
|
15611645 |
2005 |
Carcinogenesis
|
0.100 |
Biomarker
|
phenotype |
BEFREE |
Here, we discuss our recent work in the context of candidate Mad3-interacting proteins and Mad3 expression in human brain tumors that together suggest interesting insights into the role of Mad3 in cellular proliferation and tumorigenesis.
|
18235219 |
2008 |
Carcinogenesis
|
0.100 |
Biomarker
|
phenotype |
BEFREE |
Our studies support a novel role for Mad3 in cerebellar GNP proliferation and possibly tumorigenesis, and they challenge the current paradigm that Mad3 should antagonize Nmyc by competition for direct DNA binding via Max dimerization.
|
17893326 |
2007 |
Carcinogenesis
|
0.100 |
Biomarker
|
phenotype |
BEFREE |
In turn, CDK4/2 can non-canonically phosphorylate Smad3, a key TGFβ signaling intermediate, and this phosphorylation has been associated with the shift from tumor-suppressive to oncogenic TGFβ pathway action in breast oncogenesis.
|
28678584 |
2017 |
Carcinogenesis
|
0.100 |
Biomarker
|
phenotype |
BEFREE |
Therefore, through regulating different transcriptional responses, Smad3 functions as both a negative and positive regulator of carcinogenesis depending on cell type and clinical stage of the tumor.
|
17725494 |
2007 |
Carcinogenesis
|
0.100 |
Biomarker
|
phenotype |
BEFREE |
Smad3 also plays a critical role in both the tumor suppressor and pro-metastatic effects of TGF-beta in carcinogenesis.
|
16290023 |
2009 |
Carcinogenesis
|
0.100 |
Biomarker
|
phenotype |
BEFREE |
Downregulation of the TGFβ signaling through Smad3 via miRs may have a possible role in the complex regulation of signaling pathways involved in the tumorigenesis process of NFPA.
|
21063788 |
2011 |
Carcinogenesis
|
0.100 |
Biomarker
|
phenotype |
BEFREE |
TGFβ1-Smad3-Jagged1-Notch1-Slug signaling pathway takes part in tumorigenesis and progress of tongue squamous cell carcinoma.
|
26764364 |
2016 |
Carcinogenesis
|
0.100 |
Biomarker
|
phenotype |
BEFREE |
Smad3 was strongly associated with tumorigenesis and organ fibrosis.
|
31452017 |
2019 |
Carcinogenesis
|
0.100 |
Biomarker
|
phenotype |
BEFREE |
It may therefore be that, in microenvironment of cervical squamous cell carcinoma, along with the context of HPV infection, negative immune regulators FoxP3, CCL22 and CCR4 might overwhelm positive immune factors OX40L, OX40 and Smad3, giving rise to an immunosuppressive status and promote the progression of cervical carcinogenesis.
|
28086903 |
2017 |
Carcinogenesis
|
0.100 |
Biomarker
|
phenotype |
BEFREE |
SOX4 can redirect TGF-β-mediated SMAD3-transcriptional output in a context-dependent manner to promote tumorigenesis.
|
30137431 |
2018 |
Carcinogenesis
|
0.100 |
PosttranslationalModification
|
phenotype |
BEFREE |
Our results demonstrate a critical role of the counterbalance between the Smad3 C-tail and linker phosphorylation in tumorigenesis and metastasis.
|
25205100 |
2014 |
Carcinogenesis
|
0.100 |
AlteredExpression
|
phenotype |
BEFREE |
Also, Smad3 is an essential intracellular mediator of TGF-β1-induced transcriptional responses during carcinogenesis.
|
29097203 |
2017 |
Carcinogenesis
|
0.100 |
AlteredExpression
|
phenotype |
BEFREE |
Disruption of ELF results in mislocalization of Smad3 and Smad4, leading to compromised TGF-β signaling. c-Myc is an important oncogenic transcription factor, and the disruption of TGF-β signaling promotes c-Myc-induced hepatocellular carcinoma (HCC) carcinogenesis.
|
29690860 |
2018 |
Carcinogenesis
|
0.100 |
AlteredExpression
|
phenotype |
BEFREE |
These findings suggest that Smad3 expression may have a critical role in tumor suppression in the early stages of gastric carcinogenesis.
|
14647420 |
2004 |
Carcinogenesis
|
0.100 |
AlteredExpression
|
phenotype |
BEFREE |
In our previous study, we showed that long-term cigarette smoke condensate (CSC)-mediated down-regulation of Smad3 induces tumorigenesis.
|
22904681 |
2012 |
Carcinogenesis
|
0.100 |
AlteredExpression
|
phenotype |
BEFREE |
By crossing Apc(Min/+) and Smad3 mutant mice, we showed that combined activation of the Wnt pathway and attenuation of the transforming growth factor-beta (TGF-beta) pathway causes high multiplicity and rapid onset of invasive tumorigenesis almost exclusively in the distal colon, closely mimicking the familial adenomatous polyposis (FAP) disease and consisting with distinct colorectal cancer etiologies based on tumor location.
|
16951153 |
2006 |
Carcinogenesis
|
0.100 |
AlteredExpression
|
phenotype |
BEFREE |
Altogether, our results suggest that the level of Smad3 protein is an important determinant of the progression of tumorigenesis.
|
20037158 |
2010 |