CDH13, also known as T-cadherin or H-cadherin, is an atypical member of the cadherin family. It is a cell adhesion molecule anchored to the cell surface membrane via a glycosyl phosphatidyl inositol (GPI) moiety. CDH13 is involved in various biological processes, such as cell-cell interactions, synaptic plasticity, and axon guidance, and has been linked to multiple disease areas including cancer, neurodevelopmental disorders, and metabolic syndrome [3,5,9].

In a CDH13-deficient mouse model, early-life stress led to increased anxiety-like behavior, indicating a role of CDH13 in the programming of and adaptation to early-life stress [3]. In chronic myeloid leukemia (CML), activation of CDH13 expression by small RNA promoted apoptosis in BCR-ABL1-independent imatinib-resistant cells by inhibiting the NF-κB signaling pathway [2]. In clear cell renal cell carcinoma (ccRCC), CDH13 was upregulated and correlated with better survival, lower cancer stages, and lower tumor grades, and might play a role in regulating the tumor microenvironment [1]. In non-small cell lung cancer cells, CDH13 methylation was related to cisplatin resistance, and demethylation could reverse this resistance [6]. In adipose tissue, CDH13 levels were affected by obesity in mouse models and humans, and CDH13 interfered with adipocyte differentiation [4]. Also, in a Gambian population, a polymorphism in the CDH13 gene was associated with metabolic syndrome [7], and in a North Indian population, a CDH13 gene variant was associated with schizophrenia risk [8].

In conclusion, CDH13 plays essential roles in multiple biological processes and is associated with various diseases. Gene-knockout mouse models, such as the CDH13-deficient mice, have been crucial in revealing its functions in early-life stress adaptation, while other studies have explored its roles in cancer, metabolic, and neuropsychiatric diseases. Understanding CDH13 provides insights into disease mechanisms and potential therapeutic targets.

References:

1. Shao, Yuan, Li, Wenxia, Zhang, Lin, Wang, Dongwen, Wu, Bo. 2022. CDH13 is a prognostic biomarker and a potential therapeutic target for patients with clear cell renal cell carcinoma. In American journal of cancer research, 12, 4520-4544. doi:. https://pubmed.ncbi.nlm.nih.gov/36381315/

2. Su, Rui, Wen, Ziqi, Zhan, Xingri, Su, Yubin, Fei, Jia. 2024. Small RNA activation of CDH13 expression overcome BCR-ABL1-independent imatinib-resistance and their signaling pathway studies in chronic myeloid leukemia. In Cell death & disease, 15, 615. doi:10.1038/s41419-024-07006-9. https://pubmed.ncbi.nlm.nih.gov/39179585/

3. Kiser, Dominik P, Popp, Sandy, Schmitt-Böhrer, Angelika G, Lesch, Klaus-Peter, Rivero, Olga. 2018. Early-life stress impairs developmental programming in Cadherin 13 (CDH13)-deficient mice. In Progress in neuro-psychopharmacology & biological psychiatry, 89, 158-168. doi:10.1016/j.pnpbp.2018.08.010. https://pubmed.ncbi.nlm.nih.gov/30165120/

4. Göddeke, Simon, Knebel, Birgit, Fahlbusch, Pia, Ouwens, D Margriet, Kotzka, Jorg. 2018. CDH13 abundance interferes with adipocyte differentiation and is a novel biomarker for adipose tissue health. In International journal of obesity (2005), 42, 1039-1050. doi:10.1038/s41366-018-0022-4. https://pubmed.ncbi.nlm.nih.gov/29467502/

5. Takeuchi, T, Ohtsuki, Y. . Recent progress in T-cadherin (CDH13, H-cadherin) research. In Histology and histopathology, 16, 1287-93. doi:10.14670/HH-16.1287. https://pubmed.ncbi.nlm.nih.gov/11642747/

6. Wang, Yan, Zhang, Lei, Yang, Jiasheng, Li, Bin, Wang, Jun. 2018. CDH13 promoter methylation regulates cisplatin resistance of non-small cell lung cancer cells. In Oncology letters, 16, 5715-5722. doi:10.3892/ol.2018.9325. https://pubmed.ncbi.nlm.nih.gov/30344726/

7. Bojang, Kebba S, Lyrawati, Diana, Sujuti, Hidayat, Wahono, Djoko. . Association of CDH13 Gene Polymorphism and Metabolic Syndrome in Gambian Population. In Medical archives (Sarajevo, Bosnia and Herzegovina), 75, 262-268. doi:10.5455/medarh.2021.75.262-268. https://pubmed.ncbi.nlm.nih.gov/34759445/

8. Gupta, Suruchi, Priya, Indu, Arora, Manu, Mahajan, Ritu, Kapoor, Nisha. 2023. Association of the CDH13 gene variant rs9940180 with schizophrenia risk in North Indian population. In American journal of translational research, 15, 6476-6485. doi:. https://pubmed.ncbi.nlm.nih.gov/38074818/

9. Rivero, Olga, Sich, Sarah, Popp, Sandy, Franke, Barbara, Lesch, Klaus-Peter. 2012. Impact of the ADHD-susceptibility gene CDH13 on development and function of brain networks. In European neuropsychopharmacology : the journal of the European College of Neuropsychopharmacology, 23, 492-507. doi:10.1016/j.euroneuro.2012.06.009. https://pubmed.ncbi.nlm.nih.gov/22795700/