Nrcam, short for Neuronal Cell Adhesion Molecule, is a member of the L1 family of the immunoglobulin superfamily. It plays diverse roles in neural development, such as cell proliferation, differentiation, axon growth, synapse formation, and the formation of myelinated nerve structures. It functions in cell adhesion and modulates signaling pathways through multiple molecular interactions [3].

In liver cancer, Nrcam-high expressing liver cancer stem cells (LCSCs) show strong invasion and migration abilities, promoting HCC metastasis. Nrcam activates epithelial-mesenchymal transition (EMT) and metastasis-related matrix metalloproteinases (MMPs) via the MACF1-mediated β-catenin signaling pathway in LCSCs [1]. In gastric cancer, over-expression of Nrcam accelerates cell growth, migration, and infiltration, while decreasing apoptosis. It also affects EMT markers, suggesting its role as an oncogene [2]. In neuropathic pain, the differential expression of Nrcam splicing variants in dorsal root ganglions (DRGs) is crucial. Targeting Nrcam alternative splicing with antisense oligonucleotides can relieve pain hypersensitivities [4].

In summary, Nrcam is essential for neural development and is involved in multiple disease processes. Studies using gene-related models have revealed its role in cancer metastasis, gastric cancer progression, and neuropathic pain, providing insights into potential therapeutic targets for these diseases.

References:

1. Zhou, Lingyun, He, Linye, Liu, Chang-Hai, Hu, Yiguo, Tang, Hong. 2023. Liver cancer stem cell dissemination and metastasis: uncovering the role of NRCAM in hepatocellular carcinoma. In Journal of experimental & clinical cancer research : CR, 42, 311. doi:10.1186/s13046-023-02893-w. https://pubmed.ncbi.nlm.nih.gov/37993901/

2. Bai, Chen, Chen, Deng-Gang. 2022. NRCAM acts as a prognostic biomarker and promotes the tumor progression in gastric cancer via EMT pathway. In Tissue & cell, 77, 101859. doi:10.1016/j.tice.2022.101859. https://pubmed.ncbi.nlm.nih.gov/35763884/

3. Sakurai, Takeshi. 2011. The role of NrCAM in neural development and disorders--beyond a simple glue in the brain. In Molecular and cellular neurosciences, 49, 351-63. doi:10.1016/j.mcn.2011.12.002. https://pubmed.ncbi.nlm.nih.gov/22182708/

4. Liang, Lingli, Wu, Shaogen, Lin, Corinna, Chang, Yun-Juan, Tao, Yuan-Xiang. 2020. Alternative Splicing of Nrcam Gene in Dorsal Root Ganglion Contributes to Neuropathic Pain. In The journal of pain, 21, 892-904. doi:10.1016/j.jpain.2019.12.004. https://pubmed.ncbi.nlm.nih.gov/31917219/