Tacstd2-KO Mouse

Tacstd2, also known as TROP2, encodes a transmembrane glycoprotein that is an intracellular calcium signal transducer. It is involved in cell self-renewal, proliferation, invasion, and survival, and has stem-cell-like qualities [4]. Trop2 is expressed in many normal tissues, but overexpressed in numerous cancers, playing a significant role in cancer-related processes [4].

Trop2 overexpression has been associated with decreased overall survival in some solid tumors such as breast, colorectal, and pancreatic cancers [3]. The antibody-drug conjugate sacituzumab govitecan, which targets Trop2, has shown efficacy in metastatic triple-negative breast cancer, with longer progression-free and overall survival compared to single-agent chemotherapy [1,6]. Additionally, TACSTD2/Trop2 is highly expressed in advanced urothelial carcinoma, making it a suitable target for ADC treatment in most cases [5]. TACSTD2 expression is also associated with more immune cell infiltration and greater T-cell inflammation scores in some solid tumors [3]. In the context of lung infection, TACSTD2 expression increases, potentially representing a mechanism to maintain/restore epithelial barrier function and contribute to lung regeneration [2].

In conclusion, Tacstd2-encoded Trop2 plays crucial roles in both normal and diseased states. Its overexpression in various cancers makes it an important therapeutic target, as demonstrated by the effectiveness of sacituzumab govitecan. The increase in its expression during lung infection also points to its role in maintaining tissue integrity. Understanding Tacstd2 through model-based research provides insights into disease mechanisms and potential treatment strategies for cancer and lung-related diseases.

References:

1. Bardia, Aditya, Hurvitz, Sara A, Tolaney, Sara M, Itri, Loretta M, Rugo, Hope S. . Sacituzumab Govitecan in Metastatic Triple-Negative Breast Cancer. In The New England journal of medicine, 384, 1529-1541. doi:10.1056/NEJMoa2028485. https://pubmed.ncbi.nlm.nih.gov/33882206/

2. Lenárt, Sára, Lenárt, Peter, Knopfová, Lucia, Hampl, Aleš, Beneš, Petr. 2022. TACSTD2 upregulation is an early reaction to lung infection. In Scientific reports, 12, 9583. doi:10.1038/s41598-022-13637-9. https://pubmed.ncbi.nlm.nih.gov/35688908/

3. Morgenstern-Kaplan, Dan, Kareff, Samuel A, Trabolsi, Asaad, Vanderwalde, Ari M, Lopes, Gilberto. . Genomic, immunologic, and prognostic associations of TROP2 (TACSTD2) expression in solid tumors. In The oncologist, 29, e1480-e1491. doi:10.1093/oncolo/oyae168. https://pubmed.ncbi.nlm.nih.gov/38986529/

4. Shvartsur, Anna, Bonavida, Benjamin. . Trop2 and its overexpression in cancers: regulation and clinical/therapeutic implications. In Genes & cancer, 6, 84-105. doi:. https://pubmed.ncbi.nlm.nih.gov/26000093/

5. Bahlinger, Veronika, Branz, Annalena, Strissel, Pamela L, Hartmann, Arndt, Eckstein, Markus. 2024. Associations of TACSTD2/TROP2 and NECTIN-4/NECTIN-4 with molecular subtypes, PD-L1 expression, and FGFR3 mutational status in two advanced urothelial bladder cancer cohorts. In Histopathology, 84, 863-876. doi:10.1111/his.15130. https://pubmed.ncbi.nlm.nih.gov/38196202/

6. Bardia, Aditya, Mayer, Ingrid A, Vahdat, Linda T, Wegener, William A, Kalinsky, Kevin. . Sacituzumab Govitecan-hziy in Refractory Metastatic Triple-Negative Breast Cancer. In The New England journal of medicine, 380, 741-751. doi:10.1056/NEJMoa1814213. https://pubmed.ncbi.nlm.nih.gov/30786188/