ERBB1, also known as Epidermal Growth Factor Receptor (EGFR), is a protein that plays an important role in how cells communicate and function. It acts as a receiver on the surface of cells, intercepting signals from the outside environment. These signals are important for various normal bodily processes, including cell growth, division, and health.
The ERBB1 Family and Its Role
ERBB1 is a member of a family of four related receptor proteins: ErbB1, ErbB2, ErbB3, and ErbB4. These proteins are located on the outer surface of cells, where they detect external cues. ERBB1 specifically binds to signaling molecules like epidermal growth factor (EGF) and transforming growth factor-alpha (TGF-α).
ERBB1’s structure enables its function. It has an external domain that extends outside the cell to bind specific signals. A middle segment anchors the receptor within the cell membrane, while an internal domain resides inside the cell to transmit messages inward. When activated, ERBB1 participates in processes like cell proliferation, differentiation, migration, and survival.
How ERBB1 Signals Within Cells
When external signals, known as ligands, bind to the external part of ERBB1, it triggers a change. This binding causes two ERBB1 proteins to come together in a process called dimerization. This dimerization activates the receptor’s internal portion.
Upon dimerization, the internal part of ERBB1 gains a tyrosine kinase activity. This activity adds phosphate groups to specific tyrosine residues on the receptor, a process called phosphorylation. This phosphorylation initiates a cascade of internal cell signals.
These internal signals then travel through various pathways within the cell, controlling cellular processes. These processes include regulating cell growth, promoting cell division, influencing cell survival, and guiding cell movement.
ERBB1’s Connection to Disease
Malfunctions in ERBB1 can disrupt normal cellular processes, contributing to the development of various diseases, especially cancer. Overexpression is a common issue, where cells produce an abnormally high number of ERBB1 receptors. This excess makes cells overly sensitive to growth signals, leading to uncontrolled growth.
Mutations in its gene are another way ERBB1 can malfunction. These genetic changes can cause the receptor to become constantly active, even without external signals, or hypersensitive to signals. This persistent activation bypasses normal regulatory mechanisms that control cell growth and division. Gene amplification, an increase in ERBB1 gene copies, similarly results in excessive protein production, fueling uncontrolled cell growth.
These dysfunctions contribute to hallmarks of cancer, including unchecked cell growth and enhanced cell survival. ERBB1 is implicated in various cancers, such as non-small cell lung cancer, colorectal cancer, and head and neck cancers. Its abnormal activity promotes tumor growth and progression by stimulating cell division and inhibiting programmed cell death.
Targeting ERBB1 in Medical Strategies
Given ERBB1’s important role in driving disease, especially cancer, it has become a key target for drug development. Medical strategies now focus on “targeted therapies” designed to specifically block the activity of dysfunctional ERBB1, offering a more precise approach. These therapies aim to halt uncontrolled cell growth and survival.
Monoclonal antibodies are one category of ERBB1-targeting drugs. These large protein molecules bind to the external part of the ERBB1 receptor. By attaching to this external domain, they prevent natural ligands from binding and activating the receptor, blocking the initial signaling step.
Tyrosine Kinase Inhibitors (TKIs) are another class of drugs. These small molecules enter the cell and directly block the enzymatic activity of the internal ERBB1 receptor. By inhibiting this tyrosine kinase activity, TKIs prevent the receptor from phosphorylating downstream proteins and sending growth-promoting signals. Both approaches disrupt abnormal signaling pathways from ERBB1, aiming to control disease progression.