Targeting CAMK2N1/CAMK2 inhibits invasion, migration and angiogenesis of non-small cell lung cancer by promoting autophagy and apoptosis via AKT/mTOR signaling pathway

Abstract

Deregulation of calcium/calmodulin-dependent protein kinase II (CAMK2) inhibitor 1 (CAMK2N1) has been reported to be associated with the development of several malignancies. To date, there have been few studies on the role of CAMK2N1 in lung cancer. This study aimed to investigate the relationship between CAMK2N1 and the progression of non-small cell lung cancer (NSCLC). Methodological quality was assessed using the ARRIVE guidelines. CAMK2N1 was expressed at low levels in NSCLC tissues. Overexpression of CAMK2N1 in NSCLC cell lines resulted in changes such as proliferation inhibition, metastasis inhibition, autophagy increase, and apoptosis. Mechanistic studies revealed the regulatory role of CAMK2N1/CAMK2 in AKT/mTOR signaling. Upregulation of CAMK2N1 decreased the expression levels of phosphorylated calmodulin kinase 2 (p-CaMK2), phosphorylated Akt (p-Akt), and phosphorylated-mTOR (p-mTOR). In contrast, CAMK2 overexpression increased p-AKT and p-mTOR levels. Inhibition of autophagy or activation of AKT signaling reduced CAMK2N1-mediated tumor suppression. The tumorigenic ability of CAMK2N1 overexpressing cells significantly diminished in nude mice. In conclusion, this study demonstrated the cancer suppressive function of CAMK2N1 in NSCLC and showed that CAMK2N1/CAMK2 exerted anti-cancer effects by inhibiting the AKT/mTOR signaling pathway to promote autophagy.