Cd82, also known as KAI1, is a glycoprotein belonging to the tetraspanin family. It is a well-established metastasis suppressor gene that inhibits the metastasis of most tumors without affecting tumor formation [2,4,5]. Cd82 is involved in multiple biological processes such as signal transduction, cell adhesion, motility, and aggregation. It may also regulate the autotaxin-lysophosphatidic acid (ATX-LPA) axis, which is related to cell metabolism dysregulation in tumors [1].

In Cd82-deficient mice, the severity of colitis decreased, indicating that Cd82 may play a role in the pathogenesis of colitis. It was found that CD82 binds to NLRP3 and BRCC3, increasing the degradation of NLRP3 by blocking BRCC3-dependent K63-specific deubiquitination [3]. In addition, in young adult mice, overexpression of CD82 in the hippocampus induced AD-like cognitive deficits, while Cd82 -/- mice showed improved hippocampus-related memory functions, suggesting that CD82-TRPM7-Numb signaling is linked to age-related cognitive impairment [6].

In conclusion, Cd82 plays a crucial role as a metastasis suppressor in cancer, and also has implications in conditions like colitis and age-related cognitive impairment. Gene knockout mouse models, such as Cd82-deficient mice, have been instrumental in revealing these functions, providing insights into its role in disease mechanisms and potential therapeutic targets.

References:

1. Wang, Shuo, Chen, Jiang, Guo, Xiao-Zhong. . KAI1/CD82 gene and autotaxin-lysophosphatidic acid axis in gastrointestinal cancers. In World journal of gastrointestinal oncology, 14, 1388-1405. doi:10.4251/wjgo.v14.i8.1388. https://pubmed.ncbi.nlm.nih.gov/36160748/

2. Viera, Maximillian, Yip, George Wai Cheong, Shen, Han-Ming, Baeg, Gyeong Hun, Bay, Boon Huat. 2021. Targeting CD82/KAI1 for Precision Therapeutics in Surmounting Metastatic Potential in Breast Cancer. In Cancers, 13, . doi:10.3390/cancers13174486. https://pubmed.ncbi.nlm.nih.gov/34503296/

3. Kim, Jae-Sung, Kim, Hyo Keun, Lee, Joongho, Yoon, Seokhyun, Yang, Chul-Su. 2023. Inhibition of CD82 improves colitis by increasing NLRP3 deubiquitination by BRCC3. In Cellular & molecular immunology, 20, 189-200. doi:10.1038/s41423-022-00971-1. https://pubmed.ncbi.nlm.nih.gov/36600050/

4. Yan, Wei, Huang, Jinny, Zhang, Qian, Zhang, Jian. 2021. Role of Metastasis Suppressor KAI1/CD82 in Different Cancers. In Journal of oncology, 2021, 9924473. doi:10.1155/2021/9924473. https://pubmed.ncbi.nlm.nih.gov/34306081/

5. Prabhu, Venugopal Vinod, Devaraj, S Niranjali. . KAI1/CD82, Metastasis Suppressor Gene as a Therapeutic Target for Non-Small-Cell Lung Carcinoma. In Journal of environmental pathology, toxicology and oncology : official organ of the International Society for Environmental Toxicology and Cancer, 36, 269-275. doi:10.1615/JEnvironPatholToxicolOncol.2017024619. https://pubmed.ncbi.nlm.nih.gov/29283339/

6. Zhao, Yin, Kiss, Tamas, DelFavero, Jordan, Csiszar, Anna, Zhang, Xin A. 2020. CD82-TRPM7-Numb signaling mediates age-related cognitive impairment. In GeroScience, 42, 595-611. doi:10.1007/s11357-020-00166-4. https://pubmed.ncbi.nlm.nih.gov/32088828/