Cdh11, also known as cadherin-11 or OB-cadherin, is a classical cadherin belonging to a group of transmembrane proteins mainly located in adherens junctions. It mediates homophilic, Ca2+-dependent cell-cell adhesion, which is crucial for many aspects of human growth and development, and is involved in regulating stem cell fate decisions [1,4].

In disease research, knockout mouse models have provided significant insights. In pancreatic cancer, CDH11-knockout in p48-Cre;LSL-KrasG12D/+;LSL-Trp53R172H/+ (KPC) mice prolonged survival, as CDH11 expressed by cancer-associated fibroblasts (CAFs) promotes immunosuppression and extracellular matrix deposition to support tumor growth and gemcitabine resistance [5]. In liver fibrosis, CDH11-deficient mice showed decreased hepatic stellate cell (HSC) activation in vitro and less liver fibrogenesis in response to chronic CCl4-induced damage, indicating that CDH11 promotes liver fibrosis by activating HSCs [2].

In conclusion, Cdh11 is essential for cell-cell adhesion and stem cell fate regulation. Its role in promoting pancreatic cancer growth and liver fibrosis as revealed by knockout mouse models emphasizes its potential as a therapeutic target in these disease areas. Additionally, Cdh11 may act as a tumor suppressor in some cancers like tongue squamous cell carcinoma and head and neck cancer, while promoting metastasis in others, highlighting its complex role in tumorigenesis [3,6].

References:

1. Zhang, Gaoxiang, Wang, Xi, Zhang, Qingguo. 2023. Cdh11: Roles in different diseases and potential value in disease diagnosis and treatment. In Biochemistry and biophysics reports, 36, 101576. doi:10.1016/j.bbrep.2023.101576. https://pubmed.ncbi.nlm.nih.gov/38034129/

2. Ruan, Wanyuan, Pan, Runsang, Shen, Xiaoxu, Nie, Yingjie, Wu, Yayun. 2018. CDH11 promotes liver fibrosis via activation of hepatic stellate cells. In Biochemical and biophysical research communications, 508, 543-549. doi:10.1016/j.bbrc.2018.11.153. https://pubmed.ncbi.nlm.nih.gov/30509494/

3. Zheng, Bi-Tan, Li, Qing-Ling, Lan, Ting, Zheng, Da-Li, Su, Bo-Hua. 2021. CDH11 Regulates Adhesion and Transcellular Migration of Tongue Squamous Cell Carcinoma. In OncoTargets and therapy, 14, 4211-4222. doi:10.2147/OTT.S298614. https://pubmed.ncbi.nlm.nih.gov/34295163/

4. Alimperti, Stella, Andreadis, Stelios T. 2015. CDH2 and CDH11 act as regulators of stem cell fate decisions. In Stem cell research, 14, 270-82. doi:10.1016/j.scr.2015.02.002. https://pubmed.ncbi.nlm.nih.gov/25771201/

5. Peran, Ivana, Dakshanamurthy, Sivanesan, McCoy, Matthew D, Assefnia, Shahin, Byers, Stephen W. 2020. Cadherin 11 Promotes Immunosuppression and Extracellular Matrix Deposition to Support Growth of Pancreatic Tumors and Resistance to Gemcitabine in Mice. In Gastroenterology, 160, 1359-1372.e13. doi:10.1053/j.gastro.2020.11.044. https://pubmed.ncbi.nlm.nih.gov/33307028/

6. Piao, Songlin, Inglehart, Ronald C, Scanlon, Christina Springstead, Banerjee, Rajat, D'Silva, Nisha J. 2016. CDH11 inhibits proliferation and invasion in head and neck cancer. In Journal of oral pathology & medicine : official publication of the International Association of Oral Pathologists and the American Academy of Oral Pathology, 46, 89-97. doi:10.1111/jop.12471. https://pubmed.ncbi.nlm.nih.gov/27397103/