Mpzl1-KO Mouse

Mpzl1, also known as myelin protein zero-like protein 1, is a transmembrane glycoprotein involved in multiple biological processes. It participates in various signaling pathways, such as the β-catenin/TCF4, Src/Cortactin, and HGF/MET signaling pathways, which are crucial for cell proliferation, migration, invasion, and stem-like properties of cancer cells [1,2,3]. It may also be related to cell adhesion in HER2-positive breast cancer cells through forming a signaling complex with GRB2 and PTPN11 [6]. Additionally, it has been associated with schizophrenia in Han Chinese, indicating its potential role in neurological conditions [7].

In cancer research, Mpzl1 has been extensively studied. In lung adenocarcinoma, knockdown of Mpzl1 suppressed cell proliferation, migration, invasion, and the cancer stem-like properties, while overexpression had the opposite effects, and this was related to the activation of β-catenin/TCF4 signaling [1]. In non-small cell lung cancer, Mpzl1 upregulation promoted tumor metastasis and correlated with unfavorable prognosis, potentially through upregulating COL11A1 [2]. In glioblastoma, Mpzl1 acted as an HGF/MET signaling amplifier to promote cell migration and invasion [3]. In ovarian cancer, overexpression of Mpzl1 promoted cell proliferation, migration, and invasion, while its depletion inhibited these processes, with phosphorylation of Src kinase being involved [4]. In gallbladder carcinoma, Mpzl1 was highly expressed in advanced stages and promoted cell invasion, metastasis, proliferation, and survival [5]. In hepatocellular carcinoma, amplification of Mpzl1 promoted tumor cell migration through Src-mediated phosphorylation of cortactin [8].

In conclusion, Mpzl1 plays a significant role in cancer development and progression, influencing multiple cancer-related cellular functions through various signaling pathways. The studies on Mpzl1, especially those using loss-of-function models, have provided valuable insights into its role in cancer, potentially guiding the development of new cancer therapies. Additionally, its association with schizophrenia suggests its importance in understanding neurological disorders as well.

References:

1. Ge, Qiao, Zhou, Chao, Zang, Chao, Zhu, Haonan, Wang, Ansheng. 2023. MPZL1 suppresses the cancer stem-like properties of lung cancer through β-catenin/TCF4 signaling. In Functional & integrative genomics, 23, 304. doi:10.1007/s10142-023-01232-8. https://pubmed.ncbi.nlm.nih.gov/37726580/

2. Feng, Jian, Ouyang, Huiling, Wang, Jing, Chang, Cheng, Jia, Deshui. . MPZL1 upregulation promotes tumor metastasis and correlates with unfavorable prognosis in non-small cell lung cancer. In Carcinogenesis, 43, 919-929. doi:10.1093/carcin/bgac055. https://pubmed.ncbi.nlm.nih.gov/35727197/

3. Song, Haimin, Ni, Bowen, Peng, Xuetao, He, Chunming, Liu, Yawei. 2023. MPZL1 as an HGF/MET signaling amplifier promotes cell migration and invasion in glioblastoma. In Genes & diseases, 11, 101085. doi:10.1016/j.gendis.2023.101085. https://pubmed.ncbi.nlm.nih.gov/38882007/

4. Chen, Danni, Cao, Lei, Wang, Xiaojie. 2019. MPZL1 promotes tumor cell proliferation and migration via activation of Src kinase in ovarian cancer. In Oncology reports, 42, 679-687. doi:10.3892/or.2019.7199. https://pubmed.ncbi.nlm.nih.gov/31233194/

5. Liu, Xiaolei, Huang, Jia, Liu, Liguo, Liu, Rong. 2019. MPZL1 is highly expressed in advanced gallbladder carcinoma and promotes the aggressive behavior of human gallbladder carcinoma GBC‑SD cells. In Molecular medicine reports, 20, 2725-2733. doi:10.3892/mmr.2019.10506. https://pubmed.ncbi.nlm.nih.gov/31322261/

6. Beigbeder, Alice, Chartier, François J M, Bisson, Nicolas. 2017. MPZL1 forms a signalling complex with GRB2 adaptor and PTPN11 phosphatase in HER2-positive breast cancer cells. In Scientific reports, 7, 11514. doi:10.1038/s41598-017-11876-9. https://pubmed.ncbi.nlm.nih.gov/28912526/

7. He, G, Liu, X, Qin, W, Wang, P, He, L. 2006. MPZL1/PZR, a novel candidate predisposing schizophrenia in Han Chinese. In Molecular psychiatry, 11, 748-51. doi:. https://pubmed.ncbi.nlm.nih.gov/16702974/

8. Jia, Deshui, Jing, Ying, Zhang, Zhenfeng, Gu, Jianren, He, Xianghuo. 2013. Amplification of MPZL1/PZR promotes tumor cell migration through Src-mediated phosphorylation of cortactin in hepatocellular carcinoma. In Cell research, 24, 204-17. doi:10.1038/cr.2013.158. https://pubmed.ncbi.nlm.nih.gov/24296779/