epithelial-mesenchymal cell signaling
Definition
Target type: biologicalprocess
Any process that results in the transfer of information from an epithelial cell to a mesenchymal cell where it is interpreted. [GOC:dph]
Epithelial-mesenchymal transition (EMT) is a complex biological process that involves the transformation of epithelial cells into mesenchymal cells. This process is essential for normal development, wound healing, and tissue regeneration. However, aberrant EMT can contribute to the progression of various diseases, including cancer, fibrosis, and cardiovascular disease.
During EMT, epithelial cells undergo a series of morphological and functional changes. They lose their characteristic epithelial features, such as cell-cell junctions, apical-basal polarity, and epithelial-specific markers. Concomitantly, they acquire mesenchymal characteristics, including increased motility, invasiveness, and the ability to produce extracellular matrix (ECM) components.
EMT is a highly regulated process that is driven by a complex interplay of signaling pathways. The most important signaling pathways involved in EMT include:
* **TGF-β signaling:** Transforming growth factor beta (TGF-β) is a potent inducer of EMT. It activates the SMAD signaling pathway, leading to the expression of EMT-related transcription factors, such as Snail, Slug, and Twist. These transcription factors repress the expression of epithelial genes and promote the expression of mesenchymal genes.
* **Wnt signaling:** Wnt proteins are secreted signaling molecules that play a crucial role in development and tissue homeostasis. Activation of the Wnt/β-catenin signaling pathway promotes EMT by inducing the expression of genes involved in cell migration and invasion.
* **Notch signaling:** Notch signaling is another critical pathway involved in EMT. It regulates the expression of EMT-related transcription factors and contributes to the formation of mesenchymal stem cells.
* **Hedgehog signaling:** Hedgehog signaling is a developmental signaling pathway that has been implicated in EMT. Activation of this pathway promotes the expression of EMT-related genes, such as Snail and Slug.
* **PI3K/AKT signaling:** The phosphatidylinositol 3-kinase (PI3K)/AKT signaling pathway is a major regulator of cell growth, survival, and metabolism. It is also involved in EMT by promoting the expression of EMT-related genes and suppressing apoptosis.
In addition to these core signaling pathways, other factors, such as hypoxia, inflammation, and mechanical stress, can also contribute to EMT.
The molecular mechanisms underlying EMT involve a complex interplay of transcription factors, signaling molecules, and epigenetic modifications. These factors regulate the expression of genes involved in cell-cell adhesion, cell polarity, and cell motility.
Overall, EMT is a fundamental biological process that plays a crucial role in development, tissue regeneration, and disease progression. A better understanding of the molecular mechanisms underlying EMT could lead to the development of novel therapeutic strategies for a wide range of diseases.'
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Proteins (3)
| Protein | Definition | Taxonomy |
|---|---|---|
| Smoothened homolog | A protein smoothened that is encoded in the genome of human. [PRO:DNx, UniProtKB:Q99835] | Homo sapiens (human) |
| Sonic hedgehog protein | A sonic hedgehog protein that is encoded in the genome of human. [PRO:DNx, UniProtKB:Q15465] | Homo sapiens (human) |
| Bone morphogenetic protein 4 | A bone morphogenetic protein 4 that is encoded in the genome of human. [PRO:CNA, UniProtKB:P12644] | Homo sapiens (human) |
Compounds (20)
| Compound | Definition | Classes | Roles |
|---|---|---|---|
| jervine | jervine: teratogen from Veratrum grandiflorum; RN given refers to parent cpd(3beta,23beta)-isomer; structure | piperidines | |
| cyclopamine | piperidines | glioma-associated oncogene inhibitor | |
| pd 173955 | PD 173955: inhibits src family-selective tyrosine kinase; structure in first source | aryl sulfide; dichlorobenzene; methyl sulfide; pyridopyrimidine | tyrosine kinase inhibitor |
| purmorphamine | purmorphamine : A member of the class of purines that is purine substituted at C-2 by a 1-naphthyloxy group, at C-4 by a 4-morpholinophenylamino group, and at N-9 by a cyclohexyl group. purmorphamine: structure in first source | aromatic ether; morpholines; purines; secondary amino compound | osteogenesis regulator; SMO receptor agonist |
| cur 61414 | CUR 61414: inhibits the hedehog signaling pathway; structure in first source | ||
| abt 869 | aromatic amine; indazoles; phenylureas | angiogenesis inhibitor; antineoplastic agent; EC 2.7.10.1 (receptor protein-tyrosine kinase) inhibitor | |
| dorsomorphin | dorsomorphin : A pyrazolopyrimidine that is pyrazolo[1,5-a]pyrimidine which is substituted at positions 3 and 6 by pyridin-4-yl and p-[2-(piperidin-1-yl)ethoxy]phenyl groups, respectively. It is a potent, selective, reversible, and ATP-competitive inhibitor of AMPK (AMP-activated protein kinase, EC 2.7.11.31) and a selective inhibitor of bone morphogenetic protein (BMP) signaling. dorsomorphin: an AMPK inhibitor | aromatic ether; piperidines; pyrazolopyrimidine; pyridines | bone morphogenetic protein receptor antagonist; EC 2.7.11.31 {[hydroxymethylglutaryl-CoA reductase (NADPH)] kinase} inhibitor |
| lde225 | sonidegib : A member of the classo of biphenyls that is the amide obtained by formal condensation of the carboxy group of 2-methyl-4'-(trifluoromethoxy)[1,1'-biphenyl]-3-carboxylic acid with the amino group of 6-(2,6-dimethylmorpholin-4-yl)pyridin-3-amine. Used (as its phosphate salt) for treatment of locally advanced basal cell carcinoma. sonidegib: specific Smoothened/Smo antagonist | aminopyridine; aromatic ether; benzamides; biphenyls; morpholines; organofluorine compound; tertiary amino compound | antineoplastic agent; Hedgehog signaling pathway inhibitor; SMO receptor antagonist |
| gdc 0449 | HhAntag691: inhibits the hedgehog pathway and ABC transporters; has antineoplastic activity | benzamides; monochlorobenzenes; pyridines; sulfone | antineoplastic agent; Hedgehog signaling pathway inhibitor; SMO receptor antagonist; teratogenic agent |
| N-[[3-fluoro-4-[[2-(1-methyl-4-imidazolyl)-7-thieno[3,2-b]pyridinyl]oxy]anilino]-sulfanylidenemethyl]-2-phenylacetamide | thioureas | ||
| ipi-926 | IPI-926: a semisynthetic derivative of cyclopamine that is a smoothened inhibitor with antineoplastic activity; structure in first source | piperidines | |
| robotnikinin | robotnikinin: binds sonic hedgehog protein to block its signaling pathway; structure in first source | ||
| ldn 193189 | LDN 193189: inhibits bone morphogenetic protein signaling | pyrimidines | |
| gsk 1363089 | GSK 1363089: a multikinase inhibitor that acts on Met, RON, Axl, and VEGFR; structure in first source | aromatic ether | |
| tak-441 | TAK-441: structure in first source | ||
| ml347 | ML347: an ALK2 inhibitor; structure in first source | ||
| ly2940680 | |||
| 3-(2,6-dichloro-3,5-dimethoxyphenyl)-1-(6-(4-(4-ethylpiperazin-1-yl)-phenylamino)pyrimidin-4-yl)-1-methylurea | BGJ-398 : A member of the class of phenylureas that is urea in which a hydrogen attached to one of the nitrogens is replaced by a 2,6-dichloro-3,5-dimethoxyphenyl group, while the hydrogens attached to the other nitrogen are replaced by a methyl group and a 6-{[4-(4-ethylpiperazin-1-yl)phenyl]amino}pyrimidin-4-yl group. It is a potent and selective fibroblast growth factor receptor inhibitor. infigratinib: structure in first source | aminopyrimidine; dichlorobenzene; N-alkylpiperazine; N-arylpiperazine; phenylureas | antineoplastic agent; fibroblast growth factor receptor antagonist |
| cep-32496 | agerafenib: inhibitor of RAF family kinases; structure in first source | ||
| pf-5274857 | 1-(4-(5'-chloro-3,5-dimethyl-2,4'-bipyridin-2'-yl)piperazin-1-yl)-3-(methylsulfonyl)propan-1-one: a potent and selective Smoothened antagonist that penetrates the blood-brain barrier; structure in first source |