glypican 3

Target id: 2959

Nomenclature: glypican 3

Family: Tumour-associated proteins

Annotation status:  image of a grey circle Awaiting annotation/under development. Please contact us if you can help with annotation.  » Email us

   GtoImmuPdb view: OFF :     Currently no data for glypican 3 in GtoImmuPdb

Gene and Protein Information
Species TM AA Chromosomal Location Gene Symbol Gene Name Reference
Human - 603 Xq26.2 GPC3 glypican 3
Mouse - 579 X A5 Gpc3 glypican 3
Rat - 597 Xq36 Gpc3 glypican 3
Gene and Protein Information Comments
The biological relevance of the different human protein isoforms identified is unclear.
Database Links
Ensembl Gene
Entrez Gene
GenitoUrinary Development Molecular Anatomy Project
Human Protein Atlas
KEGG Gene
OMIM
RefSeq Nucleotide
RefSeq Protein
UniProtKB
Wikipedia

Download all structure-activity data for this target as a CSV file

Antibodies
Key to terms and symbols Click column headers to sort
Antibody Sp. Action Affinity Units Reference
codrituzumab Hs Binding - - 12-13
[12-13]
Physiological Functions
GPC3 acts as a negative regulator of Hedgehog (Hh) signaling during development.
Species:  Human
Tissue: 
References:  3-4,6
GPC3 can inhibit the dipeptidyl peptidase activity of CD26.
Species:  Human
Tissue: 
References:  5,11
Physiological Consequences of Altering Gene Expression
Loss-of-function mutations in GPC3 permit hyperactivation of Hegdehog (Hh) signaling, that ultimately leads to overgrowth and cancer.
Species:  Human
Tissue: 
Technique: 
References: 
Clinically-Relevant Mutations and Pathophysiology
Disease:  Simpson-Golabi-Behmel syndrome
Description: A rare X-linked recessive syndrome characterised by pre- and postnatal overgrowth, distinctive craniofacial features, variable congenital malformations, organomegaly and an increased tumour risk.
Synonyms: Golabi-Rosen syndrome
SGBS1
Simpson-Golabi-Behmel syndrome type 1
X-linked dysplasia gigantism syndrome
OMIM: 312870
Orphanet: ORPHA373
Role: 
References:  14
Gene Expression and Pathophysiology Comments
GPC3 expression can be used as a marker to distinguish hepatocellular carcinoma (GPC3+ve) from cirrhotic dysplasia (GPC3-ve) [1,10].
General Comments
Glypican 3 (GPC3) is a glycosylphosphatidylinositol-anchored proteoglycan expressed during fetal development and with high frequency on the surface of cancer cells, but rarely on normal adult cells [2], making it an ideal target for anti-cancer therapies with minimal toxicity against normal tissue [7,9,12,15], i.e. minimising on-target off-tumor activity.

Monoclonal antibodies directed at GPC3 are being developed as novel oncology drugs (e.g. Roche's codrituzumab). A bispecific mAb co-targeting GPC3 and the CD3 component of the T cell receptor complex (research code ERY974 [8]) is in Phase 1 clinical trial in patients with GPC3-positive advanced solid tumours (NCT02748837). ERY974 is an investigational cancer immunotherapy who's mechanism of action puts it in the family of mAbs referred to as T cell redirecting antibodies (or TRABs). ERY974 is designed to bring T cells in to close proximity with cancer cells to maximise antibody-activated killing capacity (both antibody induced and T cell directed) against the malignant cells.

References

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1. Anatelli F, Chuang ST, Yang XJ, Wang HL. (2008) Value of glypican 3 immunostaining in the diagnosis of hepatocellular carcinoma on needle biopsy. Am. J. Clin. Pathol.130 (2): 219-23. [PMID:18628090]

2. Baumhoer D, Tornillo L, Stadlmann S, Roncalli M, Diamantis EK, Terracciano LM. (2008) Glypican 3 expression in human nonneoplastic, preneoplastic, and neoplastic tissues: a tissue microarray analysis of 4,387 tissue samples. Am. J. Clin. Pathol.129 (6): 899-906. [PMID:18480006]

3. Bhave VS, Mars W, Donthamsetty S, Zhang X, Tan L, Luo J, Bowen WC, Michalopoulos GK. (2013) Regulation of liver growth by glypican 3, CD81, hedgehog, and Hhex. Am. J. Pathol.183 (1): 153-9. [PMID:23665349]

4. Capurro MI, Xu P, Shi W, Li F, Jia A, Filmus J. (2008) Glypican-3 inhibits Hedgehog signaling during development by competing with patched for Hedgehog binding. Dev. Cell14 (5): 700-11. [PMID:18477453]

5. Davoodi J, Kelly J, Gendron NH, MacKenzie AE. (2007) The Simpson-Golabi-Behmel syndrome causative glypican-3, binds to and inhibits the dipeptidyl peptidase activity of CD26. Proteomics7 (13): 2300-10. [PMID:17549790]

6. Filmus J, Capurro M. (2014) The role of glypicans in Hedgehog signaling. Matrix Biol.35: 248-52. [PMID:24412155]

7. Ho M, Kim H. (2011) Glypican-3: a new target for cancer immunotherapy. Eur. J. Cancer47 (3): 333-8. [PMID:21112773]

8. Ishiguro T, Sano Y, Komatsu SI, Kamata-Sakurai M, Kaneko A, Kinoshita Y, Shiraiwa H, Azuma Y, Tsunenari T, Kayukawa Y et al.. (2017) An anti-glypican 3/CD3 bispecific T cell-redirecting antibody for treatment of solid tumors. Sci Transl Med9 (410). [PMID:28978751]

9. Ishiguro T, Sugimoto M, Kinoshita Y, Miyazaki Y, Nakano K, Tsunoda H, Sugo I, Ohizumi I, Aburatani H, Hamakubo T et al.. (2008) Anti-glypican 3 antibody as a potential antitumor agent for human liver cancer. Cancer Res.68 (23): 9832-8. [PMID:19047163]

10. Jakubovic BD, Jothy S. (2007) Glypican-3: from the mutations of Simpson-Golabi-Behmel genetic syndrome to a tumor marker for hepatocellular carcinoma. Exp. Mol. Pathol.82 (2): 184-9. [PMID:17258707]

11. Khurana S, Margamuljana L, Joseph C, Schouteden S, Buckley SM, Verfaillie CM. (2013) Glypican-3-mediated inhibition of CD26 by TFPI: a novel mechanism in hematopoietic stem cell homing and maintenance. Blood121 (14): 2587-95. [PMID:23327927]

12. Nakano K, Ishiguro T, Konishi H, Tanaka M, Sugimoto M, Sugo I, Igawa T, Tsunoda H, Kinoshita Y, Habu K et al.. (2010) Generation of a humanized anti-glypican 3 antibody by CDR grafting and stability optimization. Anticancer Drugs21 (10): 907-16. [PMID:20847643]

13. Nakano K, Sugo I, Sugimoto M, Ishiguro T, Tanaka M, Iijima S. (2011) Anti-glypican 3 antibody having modified sugar chain. Patent number: US7867734 B2. Assignee: Chugai Pharmaceutical Co Ltd.. Priority date: 26/10/2004. Publication date: 11/01/2011.

14. Shi W, Filmus J. (2009) A patient with the Simpson-Golabi-Behmel syndrome displays a loss-of-function point mutation in GPC3 that inhibits the attachment of this proteoglycan to the cell surface. Am. J. Med. Genet. A149A (3): 552-4. [PMID:19215053]

15. Takai H, Kato A, Kinoshita Y, Ishiguro T, Takai Y, Ohtani Y, Sugimoto M, Suzuki M. (2009) Histopathological analyses of the antitumor activity of anti-glypican-3 antibody (GC33) in human liver cancer xenograft models: The contribution of macrophages. Cancer Biol. Ther.8 (10): 930-8. [PMID:19276671]

How to cite this page

Tumour-associated proteins: glypican 3. Last modified on 11/10/2017. Accessed on 13/12/2017. IUPHAR/BPS Guide to PHARMACOLOGY, http://www.guidetopharmacology.org/GRAC/ObjectDisplayForward?objectId=2959.