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- Table of Contents
Facts about Disintegrin and metalloproteinase domain-containing protein 9.
Cleaves and releases a number of molecules with Significant roles in tumorigenesis and angiogenesis, such as TEK, KDR, EPHB4, CD40, VCAM1 and CDH5.
May mediate cell-cell, cell- matrix interactions and regulate the motility of cells via interactions with integrins..
Human | |
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Gene Name: | ADAM9 |
Uniprot: | Q13443 |
Entrez: | 8754 |
Belongs to: |
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No superfamily |
a disintegrin and metalloproteinase domain 9 (meltrin gamma); ADAM 9; ADAM metallopeptidase domain 9 (meltrin gamma); ADAM metallopeptidase domain 9; ADAM9; Cellular disintegrin-related protein; cone rod dystrophy 9; CORD9; disintegrin and metalloproteinase domain-containing protein 9; EC 3.4.24; EC 3.4.24.-; MCMP; MCMPMDC9KIAA0021Mltng; MDC9; Meltrin gamma; Meltrin-gamma; Metalloprotease/disintegrin/cysteine-rich protein 9; MLTNG; Myeloma cell metalloproteinase
Mass (kDA):
90.556 kDA
Human | |
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Location: | 8p11.22 |
Sequence: | 8; NC_000008.11 (38996767..39105261) |
Widely expressed. Expressed in chondrocytes. Isoform 2 is highly expressed in liver and heart.
[Isoform 1]: Cell membrane; Single-pass type I membrane protein.; [Isoform 2]: Secreted.
ADAM9 is an a-secretase member. It is an important enzyme in signal transduction. This makes it a potential therapeutic target. This protein has many uses. This article will highlight some of them. Read on to learn more about ADAM9 and its uses in research. This article also explores its roles in signal transduction and its possible therapeutic uses.
ADAM9's role in neurodegenerative diseases is one of its many biological functions. It regulates the amyloid precursor (APP) cleavage, which may have implications in Alzheimer’s disease. ADAM9 contributes to embryonic growth's endocardial cushion. It also sheds the interleukin-11 (a receptor that is involved in inflammation, bone homeostasis, and bone homeostasis).
The disintegrin domain of ADAM9 consists of a zinc-binding motif. This domain acts as a ligand of several b1 integrins and is thought to play a role in cell attachment to extracellular matrix. ADAMs also have a cysteinerich domain that binds the ECM independent of integrins. It could be involved in the fusion between membranes.
ADAM9 regulates cell–cell, and cell–matrix relationships. It mediates keratinocyte migration and collagen XVII shedding. MGCs were found in aneurysmal bone cysts and giant cell tumors. This protein is essential to understanding cell-to-cell interactions, and for regulating tumorigenesis. These processes are critical for the development and implementation of new therapies.
The expression of ADAM9 is elevated in breast cancer, and has contributed to the disease's progression. It is also known to promote tumor extravasation, migration, and may play a role in trans-endothelial migrating pathways. ADAM9 knockdown lowers the expression levels of ADAM proteins MMP2and ADAM17. This has many potential clinical uses.
The ADAM9 genetic factor is crucial in the development and progression of vascular diseases in both animals and humans. Human and mouse tissues expressing ADAM9 overexpression increase angiogenesis. They also shed several angiogenesis related endothelial protein membrane proteins. This suggests it could also function as an indicator for tissue damage. These findings are promising. The future of ADAM9 Research lies in the hands and feet of researchers.
ADAM9 is also implicated in lung metastasis. Nearly 50% (of late-stage lung cancer patients) experience brain metastasis. ADAM9 has been implicated with several steps in tumor metastasis. These include adhesion of tumor cells and vascular endothelial cell migration, anoikis resistance, and adhesion of tumors to vascular cells. ADAM9 silencing reduces expression of angiopoetins2 or tPA, both essential for lung metastasis.
The ADAM9 marker peptide recognizes substrates via its cysteinerich domain and HVR. It then cleaves these receptors and releases their extracellular parts for signal transduction. Boster Bio's ADAM9Antibody Picoband can be stored at -20°C for up 1 year. It contains 4mg Trehalose. The cost of the blocker peptide depends on its length.
ADAM9 is made up of many domains. Each domain has its own function. Below is the domain structure. This structure can help you better understand how ADAM9 is activated. Each domain regulates different proteins. These proteins are not yet specific. The markers that target ADAM9 can be used to identify the types of cancers where the protein is expressed.
Multiple research studies have shown ADAM9's role in prostate cancer progression. Some have even shown that inhibition of ADAM9 enhances sensitivity to chemotherapy drugs. Furthermore, Josson et al. Josson and colleagues. also found that ADAM9 can inhibit the expression of micro-RNA and other cancer-related proteins. The knockdown of ADAM9 also inhibits the expression of MMP2 and ADAM17.
CGS27023 is an inhibitor of ADAM9. It can alter the activity by a very small molecule. The activity of ADAM10 has been inhibited by inhibitors of this enzyme. These compounds aren't very specific and can cause musculoskeletal side reactions. Many cancer drugs failed to target ADAM9 in past years. This is due in part to a lack or knowledge of the protein's mechanism of action and inhibitor specificity.
ADAM9 regulates cell-cell interactions and also contributes to the conversion monocytes into MGCs which enhances the PMN's phagocytotic activity. ADAM9-mediated neutrophil activation promoted distant metastases in mouse tumor models. Additionally, ADAM9 mediated neutrophil activation promotes wound healing as well as neuropilin-1 proteolysis.
ADAM9 is a marker found on the surface inflammatory cells that plays a role in signal transduction. It promotes Th27 cell differentiation by activating TGFb1 among other factors. ADAM9 promotes differentiation by its interaction with ICER. ADAM9 also participates in the signal transduction pathway to CD8+ cells. It performs several functions in signal transmission.
ADAM9 was found in TNBC cell line cells. It is associated with the AKT/NFKB pathway. ADAM9 expression levels in TNBC cells and non-TNBC cell lines were identical. It could be a potential therapeutic target of TNBC. We have also shown that ADAM9 inhibits cell proliferation in MCF-7 and Hs578t cells. This suggests that ADAM9 may be an important molecule in signal transmission and could be a target for treatment of TNBC.
ADAM9 mRNA levels are positively correlated to matrix metalloproteinase (9 (MMP9)) mRNA levels. ADAM9 expression is positively correlated with levels of MMP9 mRNA and MMP2. However, further studies are needed to understand the precise role of ADAM9 in signal transduction. The ADAM9 gene is regulated by several factors. Additional studies will help to determine the optimal ADAM9 concentration for early cancer diagnosis.
This study showed that ADAM-9 could influence cell migration. We placed HaCaT cells on DC-9-his-coated plastic and DC-9 -his-coated DC-9-his surfaces. Plastic cells had 0.07 mm2 migration area, while DC-9-his-coated surfaces significantly increased cell migration to 0.33mm2 after 24 hours. Our results also indicate that ADAM-9 could influence cell signal transduction through regulation of integrin binding.
The ADAM9 genes has been implicated as a cause of autoimmune disease. In mice, ADAM9 knockout cells suppress experimental autoimmune encephalomyelitis. ADAM9-deficient T lymphocytes also suppress IL-17A under Th27 polarization. We also found that ADAM9-deficient T cells decrease IL-17A production in healthy subjects. Targeting ADAM9 might be a way to alleviate Th27-dependent autoimmune disorders.
ADAM9, 10 and 11 are members the ADAM family. Their specific cleavage locations are unknown. In mouse models, knockdowns both genes resulted in the formation of a major C-terminal 10 kDa band. These results indicate ADAM9 and ADAM10 have different cleavage spots. It is not clear how ADAM9 or ADAM10 affect signal transduction within cells.
ADAM9, a key marker in TNBC cells, is important. It has been implicated within the AKT/NFKB pathway, which is often activated during the disease. TNBC cells expressed this marker at higher levels than non-TNBC cell line lines. This is a positive sign that new therapeutic approaches are possible.
The ADAM9 proteins are synthesized through the cleavage and fusion of their precursor at a consensus domain (C-SASP) as well as a pro-metalloprotease domain domain (ProMPR) domain. The mature ADAM9 protein has protease activity and is involved in cell-extracellular matrix adhesion. ADAM9 also plays a role during the progression of the disease by mediating the release EGFR ligands as well as activating the EGFR/AKT pathway. Breast cancer and prostate cancer are among the cancers with high levels of ADAM9 expression.
ADAM9 expression levels are elevated in some breast cancer cell types, including MCF-10A. It is associated with aggressive breast cancer phenotypes. The ATCC recommends a specific culture method to grow cells. This is likely to explain the increased expression of ADAM9 within MCF-10A. The ATCC recommends that MCF-10A cells be migrated by using hEGF or Mammary Epithelial Growth Medium BulletKit.
Although ADAM9 is an important therapeutic target there are still many questions. The absence of a clear mechanism to silence ADAM9 could lead to tumorigenesis and progression. However, it is important to note that ADAM9 is an integral protein that facilitates cellular adhesion. This approach should be confirmed in TNBC cells before it can be used to treat cancer.
PMID: 8647900 by Weskamp G., et al. MDC9, a widely expressed cellular disintegrin containing cytoplasmic SH3 ligand domains.
PMID: 8809033 by McKie N., et al. Cloning of a novel membrane-linked metalloproteinase from human myeloma cells.