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| | Tetraspanin 8 has a short amino- and carboxy-terminal tail, a small intracellular loop between transmembrane region 2 (TM2) and TM3, a small extracellular loop (ECL1) between TM1 and TM2 and a large extracellular loop (ECL2) between TM3 and TM4. Extracellular loop 2 contains six conserved cysteine residues (red) including the CCG motif; disulphide bonds are indicated. The transmembrane regions 1 and 4 have polar amino acids (green), the cytoplasmic domains contain palmitoylation sites (pink) and the carboxy-terminal domain contains a sorting motif (blue). |
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| Description | Tspan8 is a member of the transmembrane 4 superfamily, also known as the tetraspanin family. |
| Expression | Tetraspanin 8 is expressed in squamous epithelial cells (not epidermis), capillary endothelial cells, nerves, smooth and striated muscle cells, and subpopulations of hematopoietic progenitor cells. |
| Function | Like other tetraspanins, Tspan8 act as a "molecular facilitator" by forming a web in glycolipid-enriched membrane microdomains, called TEM (tetraspanin enriched membrane domains). Tspan8 associates with additional tetraspanins, integrins, preferentially CD49c, CD104, but also CD49d. It is directly associated with EWI-F, CD13 and intersectin 2. Via its associated molecules Tspan8 becomes involved in cell adhesion and motility as well as signal transduction. Motility promotion mostly proceeds via its association with CD104 and is in line with pronounced metastatic spread of Tspan8 overexpressing tumors as described for hepatocellular cancer. Similar to other tetraspanins, Tspan8 is abundantly present in exosomes, where it accounts via its association with CD49d for endothelial cell and endothelial cell progenitor targeting with the consequence of endothelial cell activation and endothelial cell progenitor maturation.
Regulates cell motility and survival and is involved in the promotion of angiogenesis. |
| Association between the rat homologue of CO-029, a metastasis-associated tetraspanin molecule and consumption coagulopathy. |
| Claas C, Seiter S, Claas A, Savelyeva L, Schwab M, Zoller M. |
| J Cell Biol. 1998 Apr 6;141(1):267-80. |
| PMID 9531564 |
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| Colocalization of the tetraspanins, CO-029 and CD151, with integrins in human pancreatic adenocarcinoma: impact on cell motility. |
| Gesierich S, Paret C, Hildebrand D, Weitz J, Zgraggen K, Schmitz-Winnenthal FH, Horejsi V, Yoshie O, Herlyn D, Ashman LK, Zoller M. |
| Clin Cancer Res. 2005 Apr 15;11(8):2840-52. |
| PMID 15837731 |
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| Possible involvement of tetraspanin CO-029 in hematogenous intrahepatic metastasis of liver cancer cells. |
| Kanetaka K, Sakamoto M, Yamamoto Y, Takamura M, Kanematsu T, Hirohashi S. |
| J Gastroenterol Hepatol. 2003 Nov;18(11):1309-14. |
| PMID 14535989 |
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| A complex of EpCAM, claudin-7, CD4 variant isoforms, and tetraspanins promotes colorectal cancer progression. |
| Kuhn S, Koch M, Nubel T, Ladwein M, Antolovic D, Klingbeil P, Hildebrand D, Moldenhauer G, Langbein L, Franke WW, Weitz J, Zoller M. |
| Mol Cancer Res. 2007 Jun;5(6):553-67. |
| PMID 17579117 |
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| Profiling of the tetraspanin web of human colon cancer cells. |
| Le Naour F, Andre M, Greco C, Billard M, Sordat B, Emile JF, Lanza F, Boucheix C, Rubinstein E. |
| Mol Cell Proteomics. 2006 May;5(5):845-57. Epub 2006 Feb 7. |
| PMID 16467180 |
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| Molecular cloning of cDNA for the human tumor-associated antigen CO-029 and identification of related transmembrane antigens. |
| Szala S, Kasai Y, Steplewski Z, Rodeck U, Koprowski H, Linnenbach AJ. |
| Proc Natl Acad Sci U S A. 1990 Sep;87(17):6833-7. |
| PMID 2395876 |
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| TM4SF3 promotes esophageal carcinoma metastasis via upregulating ADAM12m expression. |
| Zhou Z, Ran YL, Hu H, Pan J, Li ZF, Chen LZ, Sun LC, Peng L, Zhao XL, Yu L, Sun LX, Yang ZH. |
| Clin Exp Metastasis. 2008;25(5):537-48. Epub 2008 Mar 26. |
| PMID 18365756 |
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| A Tetraspanins: push and pull in suppressing and promoting metastasis. |
| Zoller M. |
| Nat Rev Cancer. 2009 Jan;9(1):40-55. Epub 2008 Dec 11. (REVIEW) |
| PMID 19078974 |
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