Ca2+/calmodulin-dependent protein kinase IIγ enhances stem-like traits and tumorigenicity of lung cancer cells

Abstract

Highly tumorigenic stem-like cells, considered tumor-initiating cells (TICs), are the main cause of lung cancer initiation, relapse, and drug resistance. In this study, we identified that Ca2+/calmodulin-dependent protein kinase IIγ (CaMKIIγ) was aberrantly expressed in highly tumorigenic stem-like lung cancer cells, and was also correlated with poor prognosis in human lung cancer. Functionally, CaMKIIγ enhanced stem-like traits and the tumorigenicity of lung cancer cells in an Akt- and β-catenin-dependent manner. In addition, we found that CaMKIIγ upregulated Oct4 expression via Akt-mediated histone acetylation. Taken together, our findings reveal a critical role of CaMKIIγ in regulating the stemness and tumorigenicity of lung cancer cells and offer a promising therapeutic target for TICs.

SKF-96365 activates cytoprotective autophagy to delay apoptosis in colorectal cancer cells through inhibition of the calcium/CaMKIIγ/AKT-mediated pathway

“…7F–H), similar to the effect of SKF-96365, indicating the critical role of CaMKIIγ/AKT pathway in regulation of SOCE inhibitor-activated apoptotic or autophagic signaling. A recent study further supports our hypothesis for demonstrating that CaMKIIγ directly binds to AKT for phosphorylation at Ser 473 [41]. The current study is the first report to show that CaMKIIγ is an upstream regulator of apoptosis and autophagy, and inhibition of CaMKIIγ represents a promising strategy for treatment of CRC.…”

Phosphorylation of calcium/calmodulin-stimulated protein kinase II at T286 enhances invasion and migration of human breast cancer cells

“…Recent studies have demonstrated that CaMKII is involved in controlling osteosarcoma and gastric cancer cell invasion and migration1622, and lung cancer tumourigenicity29, and we have previously implicated CaMKII in breast cancer cell proliferation1130. However, the role of CaMKII phosphorylation in cancer cell invasion and migration has not previously been explored.…”

A curcumin derivative hydrazinobenzoylcurcumin suppresses stem‐like features of glioblastoma cells by targeting Ca2+/calmodulin‐dependent protein kinase II

“…[16][17][18] To determine whether HBC affects CaMKII activity of GSCs, we tested the effect of HBC on the phosphorylation of αand γ-isoforms of CaMKII in U87MG and U373MG GSCs. [16][17][18] To determine whether HBC affects CaMKII activity of GSCs, we tested the effect of HBC on the phosphorylation of αand γ-isoforms of CaMKII in U87MG and U373MG GSCs.…”

“…10,11 Overexpression of CaM is often observed in certain tumors and several CaM-dependent enzymes are involved in tumor progression via regulation of a variety of cellular signaling pathways. 16,17 More recently, CaMKIIγ was highly activated in chronic myeloid leukemia (CML) stem cells, but not in normal blood cells. 14,15 In addition, it has been reported that γ isoform of CaMKII (CaMKIIγ) is required for maintenance of stem-like and tumorigenic properties of lung and liver cancer cells.…”