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 TACSTD2gene.[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.
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]
^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. PMID11306819. S2CID9708614.
^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]
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Ha NT, Fujiki K, Hotta Y, Nakayasu K, Kanai A (July 2000). "Q118X mutation of M1S1 gene caused gelatinous drop-like corneal dystrophy: the P501T of BIGH3 gene found in a family with gelatinous drop-like corneal dystrophy". American Journal of Ophthalmology. 130 (1): 119–120. doi:10.1016/S0002-9394(00)00596-1. PMID11004271.
Tasa G, Kals J, Muru K, Juronen E, Piirsoo A, Veromann S, et al. (November 2001). "A novel mutation in the M1S1 gene responsible for gelatinous droplike corneal dystrophy". Investigative Ophthalmology & Visual Science. 42 (12): 2762–2764. PMID11687514.
Yoshida S, Kumano Y, Yoshida A, Numa S, Yabe N, Hisatomi T, et al. (June 2002). "Two brothers with gelatinous drop-like dystrophy at different stages of the disease: role of mutational analysis". American Journal of Ophthalmology. 133 (6): 830–832. doi:10.1016/S0002-9394(02)01407-1. PMID12036680.
Ha NT, Chau HM, Cung LE, Thanh TK, Fujiki K, Murakami A, Kanai A (March 2003). "A novel mutation of M1S1 gene found in a Vietnamese patient with gelatinous droplike corneal dystrophy". American Journal of Ophthalmology. 135 (3): 390–393. doi:10.1016/S0002-9394(02)01952-9. PMID12614764.
Gires O, Eskofier S, Lang S, Zeidler R, Münz M (2003). "Cloning and characterisation of a 1.1 kb fragment of the carcinoma-associated epithelial cell adhesion molecule promoter". Anticancer Research. 23 (4): 3255–3261. PMID12926061.
Tian X, Fujiki K, Li Q, Murakami A, Xie P, Kanai A, et al. (March 2004). "Compound heterozygous mutations of M1S1 gene in gelatinous droplike corneal dystrophy". American Journal of Ophthalmology. 137 (3): 567–569. doi:10.1016/j.ajo.2003.08.008. PMID15013888.
Murakami A, Kimura S, Fujiki K, Fujimaki T, Kanai A (2004). "Mutations in the membrane component, chromosome 1, surface marker 1 (M1S1) gene in gelatinous drop-like corneal dystrophy". Japanese Journal of Ophthalmology. 48 (4): 317–320. doi:10.1007/s10384-003-0064-5. PMID15295654. S2CID28358081.
