Ca2+/calmodulin-dependent protein kinase IIγ, a critical mediator of the NF-κB network, is a novel therapeutic target in non-small cell lung cancer

• CaMKIIγ is aberrantly expressed in human NSCLC.
• CaMKIIγ promotes the growth and survival of NSCLC cells in vitro and in vivo.
• CaMKIIγ regulates direct activation of NF-κB and multiple oncogenic signaling pathways in NSCLC.
• Activated CaMKIIγ level is correlated well with the malignancy of NSCLC.

The molecular mechanism that triggers constitutive activation of nuclear factor-kappa B (NF-κB) in non-small cell lung cancer (NSCLC) remains elusive. In this present study, we demonstrated that Ca2+/calmodulin-dependent protein kinase IIγ (CaMKIIγ) is a critical molecular switch of continuous activation of NF-κB in NSCLC. We found that CaMKIIγ was aberrantly expressed in human NSCLC tissues and correlated well with the degree of malignancy. Functionally, CaMKIIγ promoted the growth and survival of NSCLC cells via direct activation of NF-κB and multiple oncogenic signaling pathways in NSCLC. Taken together, our findings described a previously uncharacterized role of CaMKIIγ in NSCLC, and suggest a novel potential therapeutic target for NSCLC treatment.