Epithelial growth factor receptor-activated nuclear factor κB signaling and its role in epithelial growth factor...

Dysregulated epithelial growth factor receptor (EGFR) signaling is directly associated with a number of cancers, such as brain, lung, and breast cancer. The downstream signaling pathways activated by EGFR have been extensively studied, such as PI3K/AKT pathway, MAPK (mitogen-activated protein kinase) pathway, and STAT (signal transducer and activator of transcription) pathway. There are growing numbers of evidence suggesting that EGFR activates nuclear factor κB (NF-κB), which is a key transcription factor controlling a variety of cellular functions. However, relatively less is known about the signal transduction mechanism that links EGFR to NF-κB activation. Here, we discuss recent progress in EGFR-induced NF-κB pathways, including the identification of CARMA3-Bcl10-MALT1 complex and protein kinase C[Latin Small Letter Open E] as 2 essential signaling components linking EGFR to the activation of IκBα kinase. In addition, we discuss the multifunctional roles of NF-κB in EGFR-associated tumors, including proliferation, tumor invasiveness, metabolism, tumor-promoting microenvironment, and EGFR tyrosine kinase inhibitor resistance.