Opcml, also known as opioid-binding protein/cell adhesion molecule-like, is a highly conserved glycosyl phosphatidylinositol (GPI)-anchored protein belonging to the IgLON family of cell adhesion molecules. It functions as a tumor suppressor, acting on receptor tyrosine kinases (RTKs) to influence cell cycle arrest, apoptosis, and migration [2,3]. It may also play roles in neural circuit development and function, and is genetically associated with schizophrenia [5,6].

In cancer research, Opcml inactivation is observed in over 80% of ovarian cancers and many other cancers. Its epigenetic silencing correlates with poor patient survival [2]. In cholangiocarcinoma, Opcml is epigenetically silenced by DNA methylation. Ectopic expression of Opcml inhibits cell proliferation by inducing apoptosis via AXL/STAT3 inactivation and suppresses cell migration and invasion via down-regulation of Rho GTPases [4]. In ovarian cancer, Opcml methylation is associated with an increased risk of the disease, especially in III/IV stages and poorly differentiated grades [1].

In conclusion, Opcml serves as a crucial tumor suppressor, with its inactivation contributing to cancer progression in multiple cancer types, especially ovarian and cholangiocarcinoma. Its role in neural-related functions also shows potential implications in neuropsychiatric disorders like schizophrenia. Studies on Opcml, including those using genetic models, help in understanding disease mechanisms and may provide new avenues for therapeutic interventions.

References:

1. Shao, Yang, Kong, Jing, Xu, Hanzi, Xie, Kaipeng, Wu, Jiangping. 2021. OPCML Methylation and the Risk of Ovarian Cancer: A Meta and Bioinformatics Analysis. In Frontiers in cell and developmental biology, 9, 570898. doi:10.3389/fcell.2021.570898. https://pubmed.ncbi.nlm.nih.gov/33777925/

2. Antony, Jane, Zanini, Elisa, Birtley, James R, Gabra, Hani, Recchi, Chiara. 2020. Emerging roles for the GPI-anchored tumor suppressor OPCML in cancers. In Cancer gene therapy, 28, 18-26. doi:10.1038/s41417-020-0187-6. https://pubmed.ncbi.nlm.nih.gov/32595215/

3. Simovic, Isidora, Castaño-Rodríguez, Natalia, Kaakoush, Nadeem O. 2019. OPCML: A Promising Biomarker and Therapeutic Avenue. In Trends in cancer, 5, 463-466. doi:10.1016/j.trecan.2019.06.002. https://pubmed.ncbi.nlm.nih.gov/31421903/

4. Khamko, Ricuphan, Daduang, Jureerut, Settasatian, Chatri, Limpaiboon, Temduang. . OPCML Exerts Antitumor Effects in Cholangiocarcinoma via AXL/STAT3 Inactivation and Rho GTPase Down-regulation. In Cancer genomics & proteomics, 18, 771-780. doi:10.21873/cgp.20296. https://pubmed.ncbi.nlm.nih.gov/34697068/

5. Zhang, Zhengrong, Ye, Maoqing, Li, Qiongwei, Li, Jun, Zhang, Dai. . The Schizophrenia Susceptibility Gene OPCML Regulates Spine Maturation and Cognitive Behaviors through Eph-Cofilin Signaling. In Cell reports, 29, 49-61.e7. doi:10.1016/j.celrep.2019.08.091. https://pubmed.ncbi.nlm.nih.gov/31577955/

6. Habicher, Judith, Sanvido, Ilaria, Bühler, Anja, Piccoli, Giovanni, Carl, Matthias. 2024. The Risk Genes for Neuropsychiatric Disorders negr1 and opcml Are Expressed throughout Zebrafish Brain Development. In Genes, 15, . doi:10.3390/genes15030363. https://pubmed.ncbi.nlm.nih.gov/38540422/