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- Table of Contents
6 Citations 16 Q&As
3 Citations 16 Q&As
2 Citations 16 Q&As
Facts about Mothers against decapentaplegic homolog 4.
Acts synergistically with SMAD1 and YY1 in bone morphogenetic protein (BMP)-mediated cardiac-specific gene expression. Binds to SMAD binding elements (SBEs) (5'-GTCT/AGAC-3') within BMP response element (BMPRE) of cardiac activating regions (By similarity).
Human | |
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Gene Name: | SMAD4 |
Uniprot: | Q13485 |
Entrez: | 4089 |
Belongs to: |
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dwarfin/SMAD family |
DPC4; DPC4SMAD, mothers against DPP homolog 4 (Drosophila); hSMAD4; JIP; MAD homolog 4; MADH4; MADH4mothers against decapentaplegic homolog 4; mothers against decapentaplegic homolog 4; mothers against decapentaplegic, Drosophila, homolog of, 4; SMAD 4; SMAD family member 4MAD, mothers against decapentaplegic homolog 4 (Drosophila); SMAD, mothers against DPP homolog 4; Smad4
Mass (kDA):
60.439 kDA
Human | |
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Location: | 18q21.2 |
Sequence: | 18; NC_000018.10 (51030213..51085042) |
Cytoplasm. Nucleus. Cytoplasmic in the absence of ligand. Migrates to the nucleus when complexed with R-SMAD (PubMed:15799969). PDPK1 prevents its nuclear translocation in response to TGF-beta (PubMed:17327236).
In this article, we will discuss how SMAD4 is a prognostic marker for cancer, regulates PAK3 levels, and inhibits the epithelial-mesenchymal transition. We will also discuss how SMAD4 is crucial for the treatment and prevention of melanoma. In addition, we will discuss how it affects miR-495 and TGFb-induced epithelial-mesenchymal transition (EMT).
A poor prognosis is often associated with patients suffering from lung cancer who have lost SMAD4. This was confirmed by 13 studies which assessed the prognostic value of SMAD4 expression in patients with lung cancer. Seven of these studies reported an overall survival (OS) and disease-free survival (DFS) rate. The I2 statistic was used to determine heterogeneity between the studies. It was interesting to note that I2 values were consistently higher than 50% in most studies.
Pancreatic ductal carcinomama can be distinguished by a rapid progression and an earlier median survival. Pancreatic adenocarcinoma can be described as a common type of cancer. Cancers that have SMAD4 mutations tend to be more aggressive and are associated with an higher risk of metastasis.
Point mutations in SMAD4 were detected in half of colorectal carcinomas. However deletions of SMAD4 within the 18q region have been found in over 40% of Dukes C colorectal tumors. In the past, studies have identified mutations in SMAD4 in as little as 10 percent of colorectal cancers. Therefore, the deletion of the SMAD4 gene in these tumors is an important factor in predicting the outcome.
Although the status of SMAD4's mutation was not established in CRLM patients, it was found that it could be a predictor of recurrence-free survival. Patients with SMAD4 mutations were less likely to need an additional Hepatoscopy. Although the precise mechanisms behind these differences remain unclear but it is possible that patients with this mutation could be more aggressive than patients without it.
Immunohistochemical staining of SMAD4 can be a common method of identifying colorectal tumors. In the study, 80 of 86 tumor samples had enough DNA to use a PCR method to amplify the SMAD4 exons 1-11. A ABI 3100 capillary sequencer was used for the sequencing. Additionally, normal tissue DNA samples were amplified to allow for comparison.
In addition, CRC alteration of the SMAD4 gene's copy status and was associated with invasive front pathological markers. These mutations were also common in patients with low or high levels of SMAD4. The overall survival rate was also associated with the status of gene copy. These results are positive. In the meantime, further studies are needed to test these results and determine the best method to utilize SMAD4 to monitor and detect the risk of developing cancer.
SMAD4 is a protein which can affect PAK3 levels within cells. It regulates miR-495 expression and miR-543 expression. The SMAD4 protein plays a crucial component in regulating JNK-Jun signal pathway. Therefore testing SMAD4 levels is a great option for cancer research. This marker has been thoroughly researched and has been proven to be extremely specific and accurate.
The SMAD4 action regulates the levels of PAK3 and provides information about the progression and metastasis that occurs in lung cancer cells. Boster Bio's SMAD4 marker has shown to be extremely efficient in detecting cancerous tumors and is a promising instrument for lung cancer research. It is an effective tool that allows cancer researchers to discover potential treatment targets. It also provides insight into the development of tumors, their progression and metastasis.
The SMAD4 protein functions as both a transcription factor and a tumor suppressor. Transcriptional factors regulate the activity of genes, while tumor suppressors stop uncontrolled cell growth. SMAD4 restoration inhibits the expression of several cancer-related genes. SMAD4 is able to target PDAC development through regulating PAK3 levels. This research could also be beneficial for other forms of cancer.
SMAD4 knockdown reduces tumor growth using human PDAC cell lines. Boster Bio's SMAD4 marker regulates PAK3 in human PDAC cells. Furthermore, it has been demonstrated that SMAD4 hinders the movement of human PDAC cells in vitro. These results are consistent with previous research showing that SMAD4 stimulates the growth of PDAC cells.
Several lines of evidence suggest that SMAD4 is linked to certain histological phenotypes found in PDAC. However, the exact molecular cause of SMAD4-dependent symptoms in PDAC remains unclear. Further research is needed to determine the precise role of this protein in cancer development. It could be a crucial part in the formation of invasive cancers.
SMAD4 and PAK3 expression is correlated in a reverse manner and this knowledge could be useful for personalized cancer treatments. As SMAD4 and PAK3 expression are both inversely related, identifying a patient's specific SMAD4 level can aid the clinician in determining the best treatment to their specific needs. However, it is important to keep in mind that these markers are not the only ones to assess the relationship between SMAD4 as well as PAK3 expression.
Smad4 negatively regulates PAK3 through transactivating miR-495 or miR-543. Both microRNAs exert opposite effects on the JNK/PAK3 pathway. These findings suggest that Smad4 might also regulate miR-495 as well as miR-543.
Overexpression of miR-495 and miR-543 reduces the activity of WT or mutant PAK3-3 UTRs. Overexpression of miR-543 and miR-495 however, hinders WT PAK3's 3'UTR activity. In mutant luciferase reporter cells, PAK3 activity was reduced by overexpression or miRs but not WT3's UTR.
SMAD4 regulates the expression of miR-495 in GC tissues. In addition to miR-495 Smad4 also regulates the expression of the TGF b/SMAD signaling pathway. These three factors impact the process of invasion, migration, and metastasis. This study shows that SMAD4 regulates miR-495 in the GC. Its regulation can have implications for cancer development.
In in vivo, miR-495 knockdown decreases metastasis. One study revealed that miR-495 overexpression slowed the growth of tumors in ectopic mice, while knockdown resulted in decreased levels of E-cadherin. MiR-362-induced suppression was prevented by knockdown of E-cadherin. MiR-495 is thought to play a key role in the formation and growth of tumors in the mouse.
The miR-362 regulates transcription of SMAD4 which is a major regulator of SMAD. SMAD4 suppresses several cancer-related proteins, such as TGF-b. It also regulates the expression of E-cadherin. The activation of SMAD4 blocks the expression of E-cadherin, an important epithelial protein.
SMAD4 overexpression blocked the WT promoter activity of ADAR1 but did not have any impact on the Site D mutant. The results also show that SMAD4 regulates miR-495 in cells. This study proves that SMAD4 is an important regulator of miR-495. However, further studies are necessary to determine the role of SMAD4 in miR-495 expression.
Both SMAD4 and CircNT5E play multiple roles in the process of breast tumorigenesis. Inhibition of miR-495 inhibits the progression of the cancer. The researchers behind the study have called circTADA2As as sponges for miR-495, and claim that they protect the genes targeted from miRNA-mediated degradation. The authors also pointed out that miR-495 is a major regulator of many cancer-related genes.
SMAD proteins are downstream of the BMP receptors and play a pivotal role in TGFb-induced EMT. The process of EMT and tissue fibrisis can be prevented through the inhibition of Smad3 nuclear translocation. Activation of Smad3 regulates the expression of TGF-b-responsive genes, including Smad3 Rac1, Smad3 and Cdc42. The activation of Smad3 increases the activity of proteins like Akt and RhoA. The activation of these proteins regulates gene expression and cellular migration.
This inhibitor targets Smad4 as well as ANCR downstream molecules that have an effect. ANCR decreases the activity of TGF-b1 and also hinders RUNX2 expression, and also increases ZO-1. ANCR blocks the phosphorylation of Smad2/3 and the production of E-cadherin. A knockdown of ANCR leads to reduced E-cadherin expression, and promotes TGF-1-induced EMT. Furthermore, SNHG7 inhibits miR-34a targets, including proliferation-related NotcH2 and apoptosis-related BCL-2. The inhibition of SMAD4 may hinder cell migration, invasion, apoptosis and tumor growth.
The Boster Bio SMAD4 inhibitor block NF-kB signaling and LINP1 expression in brain tumors. By inhibiting the actions of TGF-b, LINP1 blocks the development of NSCLC in ex vivo. It also inhibits growth and migration in A549 cells and H2299 cells.
Boster Bio's SMAD4 inhibitor also reduces the activity of lnc MMP2 by increasing the expression of MMP2. This is an essential element in the epithelial-to mechanical transition. This inhibitor also inhibits activity of TGF-b1 which is a cytokine responsible for the growth of tumors.
Boster Bio SMAD4 inhibit is a plant compound that modulates the activity of TGFB-induced epithelial me morphogenesis. Although the introduction of these compounds into clinical trials has been limited, this drug can open new avenues for treatment in cancer, fibrosing, and inflammatory diseases.
TGF-b-induced epithelial measenchymal transition (EMT) can be treated with a Recombinant SMAD4 inhibit. TGF-b in A549 cells triggers novel splicing variants (including Smad4) of Smad4. These novel splice variants could aid in the suppression of TGF-b and therefore the EMT process.
PMID: 8553070 by Hahn S.A., et al. DPC4, a candidate tumor suppressor gene at human chromosome 18q21.1.
PMID: 8774881 by Zhang Y., et al. Receptor-associated Mad homologues synergize as effectors of the TGF- beta response.
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