View source for TPBG

{{Short description|Human protein}}
{{Infobox_gene}}
{{about|the human protein|the botanical garden|Taipei Botanical Garden}}
'''Trophoblast glycoprotein''', also known as '''TPBG''', '''5T4''', '''Wnt-Activated Inhibitory Factor 1''' or '''WAIF1''', is a human protein encoded by a ''TPBG'' [[gene]].<ref name="entrez">{{cite web | title = Entrez Gene: TPBG trophoblast glycoprotein| url = https://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=7162}}</ref> TPBG is an antagonist of [[Wnt signaling pathway|Wnt/β-catenin signalling pathway]].<ref name="pmid24582434">{{cite journal | vauthors = Zhao Y, Malinauskas T, Harlos K, Jones EY | title = Structural insights into the inhibition of Wnt signaling by cancer antigen 5T4/Wnt-activated inhibitory factor 1 | journal = Structure | volume = 22 | issue = 4 | pages = 612–20 | date = Apr 2014 | pmid = 24582434 | doi = 10.1016/j.str.2014.01.009 | pmc=3988984}}</ref>
== Clinical significance ==
5T4 is an [[antigen]] expressed in a number of [[carcinoma]]s.<ref name="pmid9855063">{{cite journal | vauthors = Starzynska T, Wiechowska-Kozlowska A, Marlicz K, Bromley M, Roberts SA, Lawniczak M, Kolodziej B, Zyluk A, Stern PL | title = 5T4 oncofetal antigen in gastric carcinoma and its clinical significance | journal = European Journal of Gastroenterology & Hepatology | volume = 10 | issue = 6 | pages = 479–84 | date = Jun 1998 | pmid = 9855063 | doi = 10.1097/00042737-199806000-00008 | s2cid = 19687036 }}</ref> It is an N-glycosylated transmembrane 72 kDa [[glycoprotein]] containing eight [[leucine-rich repeat]]s.<ref name="pmid24582434"/> 5T4 is often referred to as an ''oncofetal antigen'' due to its expression in [[foetus|foetal]] [[trophoblast]] (where it was first discovered) or [[trophoblast]] [[glycoprotein]] (TPBG).
5T4 is found in [[tumor]]s including the [[Colorectal cancer|colorectal]], [[ovarian cancer|ovarian]], and [[gastric cancer|gastric]]. Its expression is used as a prognostic aid in these cases. It has very limited expression in normal tissue but is widespread in [[cancer|malignant tumours]] throughout their development. One study found that 5T4 was present in 85% of a cohort of 72 colorectal carcinomas and in 81% of a cohort of 27 gastric carcinomas.<ref>{{cite journal | vauthors = Starzynska T, Rahi V, Stern PL | title = The expression of 5T4 antigen in colorectal and gastric carcinoma | journal = British Journal of Cancer | volume = 66 | issue = 5 | pages = 867–9 | date = Nov 1992 | pmid = 1419629 | pmc = 1977963 | doi=10.1038/bjc.1992.375}}</ref>
Its confined expression appears to give 5T4 the potential to be a target for T cells in cancer [[immunotherapy]]. There has been extensive research into its role in [[antibody]]-directed immunotherapy through the use of the high-affinity [[murine]] [[monoclonal antibody]], mAb5T4, to deliver response modifiers (such as [[staphylococcus aureus]] [[superantigen]]) accurately to a tumor.
5T4 is also the target of the [[cancer vaccine]] [[TroVax]] which is in clinical trials for the treatment of a range of different [[solid tumour]] types.
== Interactions ==
TPBG has been shown to [[Protein-protein interaction|interact]] with [[GIPC1]].<ref name=pmid11798178>{{cite journal | vauthors = Awan A, Lucic MR, Shaw DM, Sheppard F, Westwater C, Lyons SA, Stern PL | title = 5T4 interacts with TIP-2/GIPC, a PDZ protein, with implications for metastasis | journal = Biochemical and Biophysical Research Communications | volume = 290 | issue = 3 | pages = 1030–6 | date = Jan 2002 | pmid = 11798178 | doi = 10.1006/bbrc.2001.6288 }}</ref>
== References ==
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== Further reading ==
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* {{cite journal | vauthors = Carsberg CJ, Myers KA, Evans GS, Allen TD, Stern PL | title = Metastasis-associated 5T4 oncofoetal antigen is concentrated at microvillus projections of the plasma membrane | journal = Journal of Cell Science | volume = 108 | issue =  8| pages = 2905–16 | date = Aug 1995 | pmid = 7593330 | series = 108 |doi=10.1242/jcs.108.8.2905 }}
* {{cite journal | vauthors = Myers KA, Rahi-Saund V, Davison MD, Young JA, Cheater AJ, Stern PL | title = Isolation of a cDNA encoding 5T4 oncofetal trophoblast glycoprotein. An antigen associated with metastasis contains leucine-rich repeats | journal = The Journal of Biological Chemistry | volume = 269 | issue = 12 | pages = 9319–24 | date = Mar 1994 | doi = 10.1016/S0021-9258(17)37110-7 | pmid = 8132670 | doi-access = free }}
* {{cite journal | vauthors = Carsberg CJ, Myers KA, Stern PL | title = Metastasis-associated 5T4 antigen disrupts cell-cell contacts and induces cellular motility in epithelial cells | journal = International Journal of Cancer | volume = 68 | issue = 1 | pages = 84–92 | date = Sep 1996 | pmid = 8895545 | doi = 10.1002/(SICI)1097-0215(19960927)68:1<84::AID-IJC15>3.0.CO;2-6 | doi-access = free }}
* {{cite journal | vauthors = King KW, Sheppard FC, Westwater C, Stern PL, Myers KA | title = Organisation of the mouse and human 5T4 oncofoetal leucine-rich glycoprotein genes and expression in foetal and adult murine tissues | journal = Biochimica et Biophysica Acta (BBA) - Gene Structure and Expression | volume = 1445 | issue = 3 | pages = 257–70 | date = Jun 1999 | pmid = 10366710 | doi = 10.1016/s0167-4781(99)00055-x }}
* {{cite journal | vauthors = Awan A, Lucic MR, Shaw DM, Sheppard F, Westwater C, Lyons SA, Stern PL | title = 5T4 interacts with TIP-2/GIPC, a PDZ protein, with implications for metastasis | journal = Biochemical and Biophysical Research Communications | volume = 290 | issue = 3 | pages = 1030–6 | date = Jan 2002 | pmid = 11798178 | doi = 10.1006/bbrc.2001.6288 }}
* {{cite journal | vauthors = Shaw DM, Woods AM, Myers KA, Westwater C, Rahi-Saund V, Davies MJ, Renouf DV, Hounsell EF, Stern PL | title = Glycosylation and epitope mapping of the 5T4 glycoprotein oncofoetal antigen | journal = The Biochemical Journal | volume = 363 | issue = Pt 1 | pages = 137–45 | date = Apr 2002 | pmid = 11903056 | pmc = 1222460 | doi = 10.1042/0264-6021:3630137 }}
* {{cite journal | vauthors = Mulryan K, Ryan MG, Myers KA, Shaw D, Wang W, Kingsman SM, Stern PL, Carroll MW | title = Attenuated recombinant vaccinia virus expressing oncofetal antigen (tumor-associated antigen) 5T4 induces active therapy of established tumors | journal = Molecular Cancer Therapeutics | volume = 1 | issue = 12 | pages = 1129–37 | date = Oct 2002 | pmid = 12481437 }}
* {{cite journal | vauthors = Otsuki T, Ota T, Nishikawa T, Hayashi K, Suzuki Y, Yamamoto J, Wakamatsu A, Kimura K, Sakamoto K, Hatano N, Kawai Y, Ishii S, Saito K, Kojima S, Sugiyama T, Ono T, Okano K, Yoshikawa Y, Aotsuka S, Sasaki N, Hattori A, Okumura K, Nagai K, Sugano S, Isogai T | title = Signal sequence and keyword trap in silico for selection of full-length human cDNAs encoding secretion or membrane proteins from oligo-capped cDNA libraries | journal = DNA Research | volume = 12 | issue = 2 | pages = 117–26 | year = 2007 | pmid = 16303743 | doi = 10.1093/dnares/12.2.117 | doi-access = free }}
* {{cite journal | vauthors = Ward CM, Eastham AM, Stern PL | title = Cell surface 5T4 antigen is transiently upregulated during early human embryonic stem cell differentiation: effect of 5T4 phenotype on neural lineage formation | journal = Experimental Cell Research | volume = 312 | issue = 10 | pages = 1713–26 | date = Jun 2006 | pmid = 16616918 | doi = 10.1016/j.yexcr.2006.02.006 }}
* {{cite journal | vauthors = Smyth LJ, Elkord E, Taher TE, Jiang HR, Burt DJ, Clayton A, van Veelen PA, de Ru A, Ossendorp F, Melief CJ, Drijfhout JW, Dermime S, Hawkins RE, Stern PL | title = CD8 T-cell recognition of human 5T4 oncofetal antigen | journal = International Journal of Cancer | volume = 119 | issue = 7 | pages = 1638–47 | date = Oct 2006 | pmid = 16646078 | doi = 10.1002/ijc.22018 | s2cid = 12989205 | doi-access = free }}
* {{cite journal | vauthors = Okazaki S, Sekizawa A, Purwosunu Y, Farina A, Wibowo N, Okai T | title = Placenta-derived, cellular messenger RNA expression in the maternal blood of preeclamptic women | journal = Obstetrics and Gynecology | volume = 110 | issue = 5 | pages = 1130–6 | date = Nov 2007 | pmid = 17978129 | doi = 10.1097/01.AOG.0000286761.11436.67 | s2cid = 24566450 }}
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[[Category:Immunology]]
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