Biology:TPBG
 Generic protein structure example |
Trophoblast glycoprotein, also known as TPBG, 5T4, Wnt-Activated Inhibitory Factor 1 or WAIF1, is a human protein encoded by a TPBG gene.[1] TPBG is an antagonist of Wnt/β-catenin signalling pathway.[2]
Clinical significance
5T4 is an antigen expressed in a number of carcinomas.[3] It is an N-glycosylated transmembrane 72 kDa glycoprotein containing eight leucine-rich repeats.[2] 5T4 is often referred to as an oncofetal antigen due to its expression in foetal trophoblast (where it was first discovered) or trophoblast glycoprotein (TPBG).
5T4 is found in tumors including the colorectal, ovarian, and gastric. Its expression is used as a prognostic aid in these cases. It has very limited expression in normal tissue but is widespread in 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.[4]
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 interact with GIPC1.[5]
References
- ↑ "Entrez Gene: TPBG trophoblast glycoprotein". https://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=7162.
- ↑ 2.0 2.1 "Structural insights into the inhibition of Wnt signaling by cancer antigen 5T4/Wnt-activated inhibitory factor 1". Structure 22 (4): 612–20. Apr 2014. doi:10.1016/j.str.2014.01.009. PMID 24582434.
- ↑ "5T4 oncofetal antigen in gastric carcinoma and its clinical significance". European Journal of Gastroenterology & Hepatology 10 (6): 479–84. Jun 1998. doi:10.1097/00042737-199806000-00008. PMID 9855063.
- ↑ "The expression of 5T4 antigen in colorectal and gastric carcinoma". British Journal of Cancer 66 (5): 867–9. Nov 1992. doi:10.1038/bjc.1992.375. PMID 1419629.
- ↑ "5T4 interacts with TIP-2/GIPC, a PDZ protein, with implications for metastasis". Biochemical and Biophysical Research Communications 290 (3): 1030–6. Jan 2002. doi:10.1006/bbrc.2001.6288. PMID 11798178.
Further reading
- "Metastasis-associated 5T4 oncofoetal antigen is concentrated at microvillus projections of the plasma membrane". Journal of Cell Science. 108 108 (8): 2905–16. Aug 1995. doi:10.1242/jcs.108.8.2905. PMID 7593330.
- "Isolation of a cDNA encoding 5T4 oncofetal trophoblast glycoprotein. An antigen associated with metastasis contains leucine-rich repeats". The Journal of Biological Chemistry 269 (12): 9319–24. Mar 1994. doi:10.1016/S0021-9258(17)37110-7. PMID 8132670.
- "Metastasis-associated 5T4 antigen disrupts cell-cell contacts and induces cellular motility in epithelial cells". International Journal of Cancer 68 (1): 84–92. Sep 1996. doi:10.1002/(SICI)1097-0215(19960927)68:1<84::AID-IJC15>3.0.CO;2-6. PMID 8895545.
- "Organisation of the mouse and human 5T4 oncofoetal leucine-rich glycoprotein genes and expression in foetal and adult murine tissues". Biochimica et Biophysica Acta (BBA) - Gene Structure and Expression 1445 (3): 257–70. Jun 1999. doi:10.1016/s0167-4781(99)00055-x. PMID 10366710.
- "5T4 interacts with TIP-2/GIPC, a PDZ protein, with implications for metastasis". Biochemical and Biophysical Research Communications 290 (3): 1030–6. Jan 2002. doi:10.1006/bbrc.2001.6288. PMID 11798178.
- "Glycosylation and epitope mapping of the 5T4 glycoprotein oncofoetal antigen". The Biochemical Journal 363 (Pt 1): 137–45. Apr 2002. doi:10.1042/0264-6021:3630137. PMID 11903056.
- "Attenuated recombinant vaccinia virus expressing oncofetal antigen (tumor-associated antigen) 5T4 induces active therapy of established tumors". Molecular Cancer Therapeutics 1 (12): 1129–37. Oct 2002. PMID 12481437.
- "Signal sequence and keyword trap in silico for selection of full-length human cDNAs encoding secretion or membrane proteins from oligo-capped cDNA libraries". DNA Research 12 (2): 117–26. 2007. doi:10.1093/dnares/12.2.117. PMID 16303743.
- "Cell surface 5T4 antigen is transiently upregulated during early human embryonic stem cell differentiation: effect of 5T4 phenotype on neural lineage formation". Experimental Cell Research 312 (10): 1713–26. Jun 2006. doi:10.1016/j.yexcr.2006.02.006. PMID 16616918.
- "CD8 T-cell recognition of human 5T4 oncofetal antigen". International Journal of Cancer 119 (7): 1638–47. Oct 2006. doi:10.1002/ijc.22018. PMID 16646078.
- "Placenta-derived, cellular messenger RNA expression in the maternal blood of preeclamptic women". Obstetrics and Gynecology 110 (5): 1130–6. Nov 2007. doi:10.1097/01.AOG.0000286761.11436.67. PMID 17978129.
 |  |
