A novel protein CMTM1-v5 specifically induced human lymphoma cells apoptosis in vitro and in vivo

Lymphoma is among the top 10 leading causes of cancer-related morbidity around the world in males, but currently, there is a lack of effective treatment strategies for this disease. Recently, we identified an alternatively spliced protein isoform, CMTM1-v5, which is significantly associated with tumor development and could serve as a potential therapeutic drug for lymphoma. Here, we showed that the overexpression of CMTM1-v5 in Raji cells or the addition of the CMTM1-v5 polypeptide to the cell culture medium induced apoptosis in vitro. During the in vivo experiments, most of the fluorescent CMTM1-v5 polypeptide converged within the tumor cells in Raji xenografts 24 h after treatment, and the injection of the polypeptide into the tail vein significantly extended survival in mice bearing Raji tumor cells. Mechanistically, the interaction between CMTM1-v5 and CAML (calcium-modulating cyclophilin ligand) negatively regulated the Ca2+ response in the ER, inducing the activation of caspases and the release of cytochrome c in mitochondria and resulting in cell apoptosis. Thus, our study provides a proof-to-concept that supports the use of CMTM1-v5 to treat lymphoma.