期刊
AGING-US
卷 14, 期 22, 页码 9264-9279出版社
IMPACT JOURNALS LLC
关键词
multiple myeloma; CD229; RAS; RASAL3
资金
- Natural Science Foundation of Jiangsu Province
- Jiangsu Postgraduate Research and Practice Innovation Program
- [BK20200097]
- [KYCX22_1977]
- [SJCX22_0773]
CD229 plays an oncogenic role in multiple myeloma by promoting cell proliferation through regulating the RAS/ERK signaling pathway.
Multiple myeloma (MM) is an incurable plasma cell malignancy, while CAR-T therapy offers a new direction for the treatment of MM. Recently, signaling lymphocytic activation molecule family 3 (CD229), a cell surface immune receptor belonging to the signaling lymphocyte activating molecule family (SLAMF), is emerging as a CAR-T therapeutic target in MM. However, a clear role of CD229 in MM remains elusive. In this study, MM patients with elevated CD229 expression achieved poor prognosis by analyzing MM clinical databases. In addition, CD229 promoted MM cell proliferation in vitro as well as in xenograft mouse model in vivo. Mechanism study revealed that CD229 promoted MM cell proliferation by regulating the RAS/ERK signaling pathway. Further exploration employed co-immunoprecipitation coupled with mass spectrometry to identify RASAL3 as an important downstream protein of CD229. Additionally, we developed a co-culture method combined with the immunofluorescence assay to confirm that intercellular tyrosine phosphorylation mediated self-activation of CD229 to activate RAS/ERK signaling pathway via interacting with RASAL3. Taken together, these findings not only demonstrate the oncogenic role of CD229 in MM cell proliferation, but also illustrate the potential of CD229 as a promising therapeutic target for MM treatment.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据