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TACSTD2

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(Redirected from TROP-2)
TACSTD2
Available structures
PDBOrtholog search: PDBe RCSB
Identifiers
AliasesTACSTD2, EGP-1, EGP1, GA733-1, GA7331, GP50, M1S1, TROP2, tumor-associated calcium signal transducer 2, tumor associated calcium signal transducer 2
External IDsOMIM: 137290; MGI: 1861606; HomoloGene: 1763; GeneCards: TACSTD2; OMA:TACSTD2 - orthologs
Orthologs
SpeciesHumanMouse
Entrez
Ensembl
UniProt
RefSeq (mRNA)

NM_002353

NM_020047

RefSeq (protein)

NP_002344

NP_064431

Location (UCSC)Chr 1: 58.58 – 58.58 MbChr 6: 67.51 – 67.51 Mb
PubMed search[3][4]
Wikidata
View/Edit HumanView/Edit Mouse

Tumor-associated calcium signal transducer 2, also known as Trop-2 and as epithelial glycoprotein-1 antigen (EGP-1)[5] is a protein that in humans is encoded by the TACSTD2 gene.[6][7][8]

This intronless gene is located at the short arm of chromosome 1 (1p32.1).[9] It encodes a carcinoma-associated antigen defined by the monoclonal antibody GA733. This antigen is a member of a family including at least two type I membrane proteins. It transduces an intracellular calcium signal and acts as a cell surface receptor.

Mutations of this gene result in gelatinous drop-like corneal dystrophy, an autosomal recessive disorder characterized by severe corneal amyloidosis leading to blindness.[8]

Trop-2 expression was originally described in trophoblasts (placenta) and fetal tissues (e.g., lung). Later, its expression was also described in the normal stratified squamous epithelium of the skin, uterine cervix, esophagus, and tonsillar crypts.[10]

Trop-2 plays a role in tumor progression by actively interacting with several key molecular signaling pathways traditionally associated with cancer development and progression. Aberrant overexpression of Trop-2 has been described in several solid cancers, such as colorectal, renal, lung, and breast cancers. Trop-2 expression has also been described in some rare and aggressive malignancies, e.g., salivary duct, anaplastic thyroid, uterine/ovarian, and neuroendocrine prostate cancers.[10] This overexpression is caused by deregulations at a transcriptional and posttranscriptional level.[9]

Trop-2 causes cancer cell growth, proliferation, invasion, migration, and survival of cancer cells, which leads to Trop-2 being associated with tumor aggressiveness and poor prognosis. This is also confirmed by the fact, that the proliferation of tumor cells is disturbed when Trop-2 is knocked down. These facts make Trop-2 a possible prognostic biomarker to identify high-risk patients, as well as an attractive therapeutic target for late-stage diseases[9]

This antigen is the target of sacituzumab govitecan and datopotamab deruxtecan (Dato-DXd),[11] both antibody-drug conjugates.

References

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  1. ^ a b c GRCh38: Ensembl release 89: ENSG00000184292Ensembl, May 2017
  2. ^ a b c GRCm38: Ensembl release 89: ENSMUSG00000051397Ensembl, May 2017
  3. ^ "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  4. ^ "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  5. ^ Immunomedics Awarded Fast Track Designation by FDA for Sacituzumab Govitecan (IMMU-132) for Triple-Negative Breast Cancer Therapy [1]
  6. ^ Linnenbach AJ, Seng BA, Wu S, Robbins S, Scollon M, Pyrc JJ, et al. (March 1993). "Retroposition in a family of carcinoma-associated antigen genes". Molecular and Cellular Biology. 13 (3): 1507–1515. doi:10.1128/MCB.13.3.1507. PMC 359462. PMID 8382772.
  7. ^ Calabrese G, Crescenzi C, Morizio E, Palka G, Guerra E, Alberti S (Apr 2001). "Assignment of TACSTD1 (alias TROP1, M4S1) to human chromosome 2p21 and refinement of mapping of TACSTD2 (alias TROP2, M1S1) to human chromosome 1p32 by in situ hybridization". Cytogenetics and Cell Genetics. 92 (1–2): 164–165. doi:10.1159/000056891. PMID 11306819. S2CID 9708614.
  8. ^ a b "Entrez Gene: TACSTD2 tumor-associated calcium signal transducer 2".
  9. ^ a b c Wen, Ying; Ouyang, Dengjie; Zou, Qiongyan; Chen, Qitong; Luo, Na; He, Hongye; Anwar, Munawar; Yi, Wenjun (December 2022). "A literature review of the promising future of TROP2: a potential drug therapy target". Annals of Translational Medicine. 10 (24): 1403. doi:10.21037/atm-22-5976. ISSN 2305-5839. PMC 9843409. PMID 36660684.
  10. ^ a b Vranic S, Gatalica Z (February 2022). "Trop-2 protein as a therapeutic target: A focused review on Trop-2-based antibody-drug conjugates and their predictive biomarkers". Bosnian Journal of Basic Medical Sciences. 22 (1): 14–21. doi:10.17305/bjbms.2021.6100. PMC 8860310. PMID 34181512.
  11. ^ Datopotamab deruxtecan showed clinically meaningful overall survival improvement vs. chemotherapy in patients with advanced nonsquamous non-small cell lung cancer in TROPION-Lung01 Phase III trial[2]

Further reading

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