LTF (lactotransferrin, also known as lactoferrin) is a key component of innate 
immune defense. It has recently been found to have anti-tumor and 
anti-metastatic activity in different cancers. We previously reported LTF to be 
the most significantly downregulated gene in nasopharyngeal carcinoma (NPC) 
specimens relative to normal nasopharyngeal epithelial tissues, and it was also 
negatively associated with the progression and metastasis of NPC. However, the 
mechanism underlying this remains unclear. In the current study, we revealed 
that LTF can suppress 3-phosphoinositide-dependent protein kinase 1 expression 
via the mitogen-activated protein kinase/c-Jun pathway and thus repress AKT 
signaling. We also showed that LTF interacts with keratin 18 (K18) and so blocks 
the formation of the K18-14-3-3 complex, leading to downregulation of 
K18-mediated AKT activation. Thus, LTF suppresses AKT signaling by two separate 
mechanisms, leading to inhibition of NPC tumorigenesis. This is the first report 
on the tumor suppressive effects of LTF through repression of AKT signaling in 
NPC. It suggests that both LTF and AKT signaling merit further study in the 
field of NPC research.