Publication date: 10 July 2017
Source:Cancer Cell, Volume 32, Issue 1
Author(s): Ying Gu, Jiawei Zhang, Xiaoxiao Ma, Byung-wook Kim, Hailong Wang, Jinfan Li, Yi Pan, Yang Xu, Lili Ding, Lu Yang, Chao Guo, Xiwei Wu, Jun Wu, Kirk Wu, Xiaoxian Gan, Gang Li, Ling Li, Stephen J. Forman, Wing-Chung Chan, Rongzhen Xu, Wendong Huang
Although high c-Myc protein expression is observed alongside MYC amplification in some cancers, in most cases protein overexpression occurs in the absence of gene amplification, e.g., T cell lymphoma (TCL). Here, Ca2+/calmodulin-dependent protein kinase II γ (CAMKIIγ) was shown to stabilize the c-Myc protein by directly phosphorylating it at serine 62 (S62). Furthermore, CAMKIIγ was shown to be essential for tumor maintenance. Inhibition of CAMKIIγ with a specific inhibitor destabilized c-Myc and reduced tumor burden. Importantly, high CAMKIIγ levels in patient TCL specimens correlate with increased c-Myc and pS62-c-Myc levels. Together, the CAMKIIγ:c-Myc axis critically influences the development and maintenance of TCL and represents a potential therapeutic target for TCL.
T cell lymphomas (TCL) overexpress the c-Myc protein without MYC rearrangements or amplification. Gu et al. show that CAMKIIγ stabilizes c-Myc by phosphorylating it at Ser62, that the CAMKIIγ level positively correlates with the c-Myc level in patient TCL, and that inhibition of CAMKIIγ reduces TCL burden in mice.