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E-cadherin
Cadherin-1 or Epithelial cadherin (E-cadherin), is a protein that in humans is encoded by the ''CDH1'' gene (not to be confused with the APC/C activator protein CDH1). Mutations are correlated with Hereditary diffuse gastric cancer, gastric, Hereditary lobular breast cancer, breast, colorectal, thyroid, and ovarian cancers. CDH1 has also been designated as CD324 (cluster of differentiation 324). It is a tumor suppressor gene. History The discovery of cadherin cell-cell adhesion proteins is attributed to Masatoshi Takeichi, whose experience with adhering epithelial cells began in 1966. His work originally began by studying lens differentiation in chicken embryos at Nagoya University, where he explored how retinal cells regulate lens fiber differentiation. To do this, Takeichi initially collected media that had previously cultured neural retina cells (CM) and suspended lens epithelial cells in it. He observed that cells suspended in the CM media had delayed attachment compared to ...
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Cadherin
Cadherins (named for "calcium-dependent adhesion") are cell adhesion molecules important in forming adherens junctions that let cells adhere to each other. Cadherins are a class of type-1 transmembrane proteins, and they depend on calcium (Ca2+) ions to function, hence their name. Cell-cell adhesion is mediated by extracellular cadherin domains, whereas the Cadherin cytoplasmic region, intracellular cytoplasmic tail associates with numerous adaptors and signaling proteins, collectively referred to as the cadherin adhesome. Background The cadherin family is essential in maintaining cell-cell contact and regulating cytoskeletal complexes. The cadherin superfamily includes cadherins, protocadherins, desmogleins, desmocollins, and more. In structure, they share ''cadherin repeats'', which are the extracellular Ca2+-binding domains. There are multiple classes of cadherin molecules, each designated with a prefix for tissues with which it associates. Classical cadherins maintain the ton ...
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Beta-catenin
Catenin beta-1, also known as β-catenin (''beta''-catenin), is a protein that in humans is encoded by the ''CTNNB1'' gene. β-Catenin is a dual function protein, involved in regulation and coordination of cell–cell adhesion and gene transcription. In humans, the CTNNB1 protein is encoded by the ''CTNNB1'' gene. In ''Drosophila'', the homologous protein is called ''armadillo''. β-catenin is a subunit of the cadherin protein complex and acts as an intracellular signal transducer in the Wnt signaling pathway. It is a member of the catenin protein family and homologous to Plakoglobin, γ-catenin, also known as plakoglobin. β-Catenin is widely expressed in many tissues. In cardiac muscle, β-catenin localizes to adherens junctions in intercalated disc structures, which are critical for electrical and mechanical coupling between adjacent cardiomyocytes. Mutations and overexpression of β-catenin are associated with many cancers, including hepatocellular carcinoma, colorectal cance ...
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P120-catenin
p120 catenin, or simply p120, also called catenin delta-1, is a protein that in humans is encoded by the ''CTNND1'' gene. Function This gene encodes a member of the Armadillo protein family, which function in adhesion between cells and signal transduction. Multiple translation initiation codons and alternative splicing result in many different isoforms being translated. Not all of the full-length natures of the described transcript variants have been determined. Clinical significance Either loss or cytoplasmic localization of p120 is a common feature in the progression of several types of carcinoma. Interactions CTNND1 has been shown to interact with: * β-Catenin, * CDH1, * CDH2, * Collagen, type XVII, alpha 1, * Cortactin, * FYN, * MUC1, * Nephrin, * PSEN1, * PTPN6, * PTPRJ, * PTPRM, * VE-cadherin, * YES1 Tyrosine-protein kinase Yes is a Enzyme, non-receptor tyrosine kinase that in humans is encoded by the ''YES1'' gene. This gene is the cel ...
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CTNND1
p120 catenin, or simply p120, also called catenin delta-1, is a protein that in humans is encoded by the ''CTNND1'' gene In biology, the word gene has two meanings. The Mendelian gene is a basic unit of heredity. The molecular gene is a sequence of nucleotides in DNA that is transcribed to produce a functional RNA. There are two types of molecular genes: protei .... Function This gene encodes a member of the Armadillo protein family, which function in adhesion between cells and signal transduction. Multiple translation initiation codons and alternative splicing result in many different isoforms being translated. Not all of the full-length natures of the described transcript variants have been determined. Clinical significance Either loss or cytoplasmic localization of p120 is a common feature in the progression of several types of carcinoma. Interactions CTNND1 has been shown to interact with: * β-Catenin, * CDH1, * CDH2, * Collagen, type XVII, alpha 1, ...
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CBLL1
The E3 ubiquitin-protein ligase Hakai (HAKAI) also known as Casitas B-lineage lymphoma-transforming sequence-like protein 1 (CBLL1) is an enzyme that in humans is encoded by the CBLL1 gene. This gene encodes an E3 ubiquitin ligase for the E-cadherin complex and mediates its ubiquitination, endocytosis, and degradation in the lysosomes. The encoded protein contains a RING-finger domain and is also thought to have a role in control of cell proliferation. Function Hakai functions as a RING finger domain-containing E3 ubiquitin ligase for E-cadherin. Hakai mediates E-cadherin ubiquitination and its degradation by proteasomes. "Hakai" means "destruction" in Japanese. Proteosomal degradation of E-cadherin can be regulated by phosphorylation. The Hakai binding site is a part of the E-cadherin cytoplasmic domain that contains several tyrosines. Tyrosine kinases such as Src and Met can phosphorylate E-cadherin and enhance Hakai binding to E-cadherin. Two lysine Lysine (symbol L ...
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Catenin (cadherin-associated Protein), Alpha 1
αE-catenin, also known as Catenin alpha-1 is a protein that in humans is encoded by the ''CTNNA1'' gene. αE-catenin is highly expressed in cardiac muscle and localizes to adherens junctions at intercalated disc structures where it functions to mediate the anchorage of actin filaments to the sarcolemma. αE-catenin also plays a role in tumor metastasis and skin cell function. Structure Human αE-catenin protein is 100.0 kDa and 906 amino acids. Catenins (α,β,and γ (also known as plakoglobin)) were originally identified in complex with E-cadherin, an epithelial cell adhesion protein. αE-catenin is highly expressed in cardiac muscle and is homologous to the protein vinculin; however, aside from vinculin, αE-catenin has no homology to established actin-binding proteins. The N-terminus of αE-catenin binds β-catenin or γ-catenin/plakoglobin, and the C-terminus binds actin directly or indirectly via vinculin or α-actinin. Function Though αE-catenin exhibits substant ...
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Hereditary Lobular Breast Cancer
Hereditary lobular breast cancer is a rare inherited cancer predisposition associated with pathogenic CDH1 (gene) germline mutations, and without apparent correlation with the hereditary diffuse gastric cancer syndrome. Research studies identified novel CDH1 germline variants in women with diagnosed lobular breast cancer (in invasive and/or ''in situ'' histotype) and without any family history of gastric carcinoma. Firstly, in 2018 Giovanni Corso et al. defined this syndrome as a new cancer predisposition and the Authors suggested additional clinical criteria to testing CDH1 in lobular breast cancer patients. In 2020, the International Gastric Cancer Linkage Consortium recognized officially that the hereditary lobular breast cancer is a possible independent syndrome. To date, there are reported about 40 families clustering for lobular breast cancer and associated with CDH1 germline mutations but without association with diffuse gastric cancer. Other recent studies demonstrated a ...
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Hereditary Diffuse Gastric Cancer
Hereditary diffuse gastric cancer (HDGC) is an inherited genetic syndrome most often caused by an inactivating mutation in the E-cadherin gene (''CDH1'') located on chromosome 16. Individuals who inherit an inactive copy of the ''CDH1'' gene are at significantly elevated risk for developing stomach cancer. For this reason, individuals with these mutations will often elect to undergo prophylactic gastrectomy, or a complete removal of the stomach to prevent this cancer. Mutations in ''CDH1'' are also associated with high risk of lobular breast cancers, and may be associated with a mildly elevated risk of colon cancer. The most common form of stomach cancer associated with ''CDH1'' mutations is diffuse-type adenocarcinoma. An estimated 70% of males and 56% of females who inherit an inactivating ''CDH1'' mutation will develop this form of cancer by age 80. Female patients are also estimated to have a 42% lifetime risk of developing lobular breast cancer. The median age of gastric ...
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Blastula
Blastulation is the stage in early animal embryonic development that produces the blastula. In mammalian development, the blastula develops into the blastocyst with a differentiated inner cell mass and an outer trophectoderm. The blastula (from Greek '' βλαστός'' ( meaning ''sprout'')) is a hollow sphere of cells known as blastomeres surrounding an inner fluid-filled cavity called the blastocoel. Embryonic development begins with a sperm fertilizing an egg cell to become a zygote, which undergoes many cleavages to develop into a ball of cells called a morula. Only when the blastocoel is formed does the early embryo become a blastula. The blastula precedes the formation of the gastrula in which the germ layers of the embryo form. A common feature of a vertebrate blastula is that it consists of a layer of blastomeres, known as the blastoderm, which surrounds the blastocoel. In mammals, the blastocyst contains an embryoblast (or inner cell mass) that will eventuall ...
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CDH3 (gene)
Cadherin-3, also known as P-Cadherin, is a protein that in humans is encoded by the ''CDH3'' gene. Function This gene is a classical cadherin Cadherins (named for "calcium-dependent adhesion") are cell adhesion molecules important in forming adherens junctions that let cells adhere to each other. Cadherins are a class of type-1 transmembrane proteins, and they depend on calcium (Ca2+) ... from the cadherin superfamily. The encoded protein is a calcium-dependent cell-cell adhesion glycoprotein composed of five extracellular cadherin repeats, a transmembrane region and a highly conserved cytoplasmic tail. This gene is located in a six-cadherin cluster in a region on the long arm of chromosome 16 that is involved in loss of heterozygosity events in breast and prostate cancer. In addition, aberrant expression of this protein is observed in cervical adenocarcinomas. Clinical significance Mutations in this gene have been associated with congenital hypotrichosis with juvenile ...
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C-Met
Hepatocyte growth factor receptor (HGF receptor) is a protein that in humans is encoded by the ''MET'' gene. The protein possesses tyrosine kinase activity. The primary single chain precursor protein is post-translationally cleaved to produce the alpha and beta subunits, which are disulfide linked to form the mature receptor. HGF receptor is a single pass tyrosine kinase receptor essential for embryonic development, organogenesis and wound healing. Hepatocyte growth factor/Scatter Factor (HGF/SF) and its splicing isoform (NK1, NK2) are the only known ligands of the HGF receptor. MET is normally expressed by cells of epithelial origin, while expression of HGF/SF is restricted to cells of mesenchymal origin. When HGF/SF binds its cognate receptor MET it induces its dimerization through a not yet completely understood mechanism leading to its activation. Sometimes MET is misunderstood as of an abbreviation of Mesenchymal-Epithelial Transition. It is incorrect. The three letters ...
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