Cdh12, also known as Cadherin 12 or N-Cadherin 2, encodes a type II classical cadherin from the cadherin superfamily, which mediates calcium-dependent cell adhesion. It is involved in multiple biological processes, such as maintaining tissue architecture, cell-cell interactions during embryogenesis, tissue morphogenesis, and differentiation [4,8,9].

In cancer research, CDH12-enriched tumors in bladder cancer define patients with poor outcome following surgery with or without neoadjuvant chemotherapy, but exhibit superior response to immune checkpoint therapy. Molecularly, the CDH12 population resembles an undifferentiated state with aggressive biology, including chemoresistance [1]. In thyroid carcinoma, FTO/IGF2BP2-mediated N6 methyladenosine modification affects CDH12, which promotes invasion and metastasis through the epithelial-to-mesenchymal transition (EMT) pathway [2]. In salivary adenoid cystic carcinoma, CDH12 promotes invasion and metastasis, as its overexpression enhances, and knockdown inhibits, the invasive and migratory ability of cells [4]. In breast cancer, chemotherapy-induced executioner caspase activation increases CDH12 expression through epigenetic de-repression, enhancing breast cancer malignancy [6]. In colorectal cancer, CDH12 promotes proliferation, migration, invasion, adhesion, and angiogenesis, suggesting it may be an oncogene [8].

In other diseases, CDH12 is a candidate gene for kidney injury in posterior urethral valve cases [3]. In endometriosis-related infertility, CDH12 levels are higher in patients with infertility or primary infertility [5]. In a Tunisian family, a novel CDH12 variant was identified as a potential candidate for an autosomal dominant form of transgrediens and progrediens palmoplantar keratoderma [7]. In neurons, CDH12 promotes neurite outgrowth through the PKA/Rac1/Cdc42 pathway [9]. Overall, Cdh12 plays diverse and significant roles in multiple biological processes and disease conditions, and its study in various models helps to understand these functions better.

References:

1. Gouin, Kenneth H, Ing, Nathan, Plummer, Jasmine T, Knott, Simon R V, Theodorescu, Dan. 2021. An N-Cadherin 2 expressing epithelial cell subpopulation predicts response to surgery, chemotherapy and immunotherapy in bladder cancer. In Nature communications, 12, 4906. doi:10.1038/s41467-021-25103-7. https://pubmed.ncbi.nlm.nih.gov/34385456/

2. Chen, Zuyao, Zhong, Xiaolin, Xia, Min, Zu, Xuyu, Zhong, Jing. 2024. FTO/IGF2BP2-mediated N6 methyladenosine modification in invasion and metastasis of thyroid carcinoma via CDH12. In Cell death & disease, 15, 733. doi:10.1038/s41419-024-07097-4. https://pubmed.ncbi.nlm.nih.gov/39379360/

3. van der Zanden, Loes F M, van Rooij, Iris A L M, Quaedackers, Josine S L T, Roeleveld, Nel, Feitz, Wout F J. 2021. CDH12 as a Candidate Gene for Kidney Injury in Posterior Urethral Valve Cases: A Genome-wide Association Study Among Patients with Obstructive Uropathies. In European urology open science, 28, 26-35. doi:10.1016/j.euros.2021.04.001. https://pubmed.ncbi.nlm.nih.gov/34337522/

4. Wang, Jin-Feng, She, Lin, Su, Bo-Hua, Zheng, Da-Li, Lu, You-Guang. 2011. CDH12 promotes the invasion of salivary adenoid cystic carcinoma. In Oncology reports, 26, 101-8. doi:10.3892/or.2011.1286. https://pubmed.ncbi.nlm.nih.gov/21573496/

5. Goławski, Ksawery, Soczewica, Robert, Kacperczyk-Bartnik, Joanna, Żórawski, Marcin, Laudański, Piotr. 2022. The Role of Cadherin 12 (CDH12) in the Peritoneal Fluid among Patients with Endometriosis and Endometriosis-Related Infertility. In International journal of environmental research and public health, 19, . doi:10.3390/ijerph191811586. https://pubmed.ncbi.nlm.nih.gov/36141853/

6. Wang, Yuxing, Wang, Ru, Liu, Xiaohe, Wang, Molin, Sun, Gongping. 2023. Chemotherapy-induced executioner caspase activation increases breast cancer malignancy through epigenetic de-repression of CDH12. In Oncogenesis, 12, 34. doi:10.1038/s41389-023-00479-x. https://pubmed.ncbi.nlm.nih.gov/37355711/

7. Charfeddine, Cherine, Dallali, Hamza, Abdessalem, Ghaith, Abdelhak, Sonia, Mokni, Mourad. 2020. Identification of a CDH12 potential candidate genetic variant for an autosomal dominant form of transgrediens and progrediens palmoplantar keratoderma in a Tunisian family. In Journal of human genetics, 65, 397-410. doi:10.1038/s10038-019-0711-4. https://pubmed.ncbi.nlm.nih.gov/31911611/

8. Zhao, Jingkun, Li, Pu, Feng, Hao, Zhu, Zhenggang, Lu, Aiguo. 2013. Cadherin-12 contributes to tumorigenicity in colorectal cancer by promoting migration, invasion, adhersion and angiogenesis. In Journal of translational medicine, 11, 288. doi:10.1186/1479-5876-11-288. https://pubmed.ncbi.nlm.nih.gov/24237488/

9. Guo, Beibei, Qi, Mengwei, Huang, Shuai, Guan, Tuchen, Liu, Yan. 2021. Cadherin-12 Regulates Neurite Outgrowth Through the PKA/Rac1/Cdc42 Pathway in Cortical Neurons. In Frontiers in cell and developmental biology, 9, 768970. doi:10.3389/fcell.2021.768970. https://pubmed.ncbi.nlm.nih.gov/34820384/