Related Experiment Video
Updated: Nov 16, 2025
Studying TGF-β Signaling and TGF-β-induced Epithelial-to-mesenchymal Transition in Breast Cancer and Normal Cells
Published on: October 27, 2020
Epithelial growth factor receptor-activated nuclear factor κB signaling and its role in epithelial growth factor
1From the Department of Molecular and Cellular Oncology, The University of Texas MD Anderson Cancer Center; and Cancer Biology Program, The University of Texas Graduate School of Biomedical Sciences, Houston, TX.
Abstract:
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.
Insights
Epidermal growth factor receptor (EGFR) activates nuclear factor kappa B (NF-κB) through CARMA3-Bcl10-MALT1 and protein kinase C. This pathway influences cancer progression and treatment resistance.
Area of Science:
- Oncology
- Molecular Biology
- Cell Signaling
Background:
- Dysregulated epidermal growth factor receptor (EGFR) signaling is implicated in various cancers, including brain, lung, and breast cancer.
- While downstream pathways like PI3K/AKT and MAPK are well-studied, the link between EGFR and nuclear factor κB (NF-κB) activation is less understood.
Purpose of the Study:
- To elucidate the signal transduction mechanisms connecting EGFR to NF-κB activation.
- To discuss the roles of NF-κB in EGFR-associated tumors.
Main Methods:
- Review of recent progress in EGFR-induced NF-κB pathways.
- Identification of key signaling components linking EGFR to IκBα kinase activation.
Main Results:
- The CARMA3-Bcl10-MALT1 complex and protein kinase C are identified as essential signaling components.
- These components link EGFR to the activation of IκBα kinase, a crucial step in NF-κB activation.
Conclusions:
- NF-κB plays multifaceted roles in EGFR-associated tumors, including proliferation, invasiveness, metabolism, and microenvironment modulation.
- Understanding this pathway is critical for addressing EGFR tyrosine kinase inhibitor resistance.
