Research Paper Volume 12, Issue 13 pp 13668—13683
CAMKIIγ is a targetable driver of multiple myeloma through CaMKIIγ/ Stat3 axis
- 1 Department of Hematology, Key Laboratory of Cancer Prevention and Intervention, China National Ministry of Education, Key Laboratory of Molecular Biology in Medical Sciences, Zhejiang Province, The Second Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou 310000, Zhejiang, China
- 2 Cancer Institute of Zhejiang University, Hangzhou 310000, Zhejiang, China
Received: February 25, 2020 Accepted: April 28, 2020 Published: July 13, 2020https://doi.org/10.18632/aging.103490
How to Cite
Copyright © 2020 Yang et al. This is an open-access article distributed under the terms of the Creative Commons Attribution (CC BY) 3.0 License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
Aberrant activation of CAMKIIγ has been linked to leukemia and T-cell lymphoma, but not multiple myeloma (MM). The purpose of this study was to explore the role of CaMKIIγ in the pathogenesis and therapy of MM. In this study, we found that CaMKIIγ was aberrantly activated in human MM and its expression level was positively correlated with malignant progression and poor prognosis. Ectopic expression of CaMKIIγ promoted cell growth, colony formation, cell cycle progress and inhibited apoptosis of MM cell lines, whereas, knockdown of CAMKIIγ expression suppressed MM cell growth in vitro and in vivo. Mechanically, we observed that CaMKIIγ overexpression upregulated p-ERK and p-Stat3 levels and suppression of CaMKIIγ had opposite effects. CaMKIIγ is frequently dysregulated in MM and plays a critical role in maintaining MM cell growth through upregulating STAT3 signaling pathway. Furthermore, our preclinical studies suggest that CaMKIIγ is a potential therapeutic target in MM, and could be intervened pharmacologically by small-molecule berbamine analogues.
MM: multiple myeloma; PI: proteasome inhibitors; IMiDs: immunomodulatory agents; CAMKII: Ca2+/calmodulin–dependent protein kinase II Ca2+/calmodulin–dependent protein kinase II; BBM: berbamine; LSC: leukemia stem cells; FFPE: formalin-fixed paraffin-embedded; IHC: Immunohistochemistry; IF: Immunofluorescence histochemistry.