ERBB SIGNALING PATHWAY: A CRITICAL REGULATOR OF CELLULAR FUNCTIONS

The ERBB signaling pathway, also known as the Epidermal Growth Factor Receptor (EGFR) family, plays a crucial role in regulating a variety of cellular processes, including growth, survival, differentiation, and migration. This pathway consists of four receptors ERBB1 (EGFR), ERBB2 (HER2), ERBB3 (HER3), and ERBB4 (HER4) which interact with several ligands like EGF, TGF-alpha, and heregulin to trigger complex intracellular signaling cascades.

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ErbB-signaling-pathway-receptors and their ligands

ErbB receptors and their ligands. ErbB2 has no known ligand, while ErbB3 lacks intrinsic kinase activity (indicated by a cross). Following ligand binding, the receptors activate several downstream signaling pathways thereby regulating cell growth, proliferation, and survival. These processes play an important role in development, wound healing and tissue regeneration. EGF, epidermal growth factor; TGFα, transforming growth factor-α; EPG, epigen; AREG, amphiregulin; EREG, epiregulin; BC, betacellulin; HB-EGF, heparin-binding EGF-like growth factor; NRG1-4, neuregulin 1-4; STAT, signal transducer and activator of transcription; MAPK/ERK, mitogen-activated protein kinase/extracellular signal-regulated kinase; PIK3/Akt, phosphoinositide 3-kinase/protein kinase B; PLCγ, phospholipase Cγ.

KEY COMPONENTS OF ERBB SIGNALING PATHWAY

EGFR (ERBB1): The activation of EGFR leads to the recruitment of adaptor proteins and the initiation of downstream signaling, promoting cell survival and proliferation.
HER2 (ERBB2): Often overexpressed in cancer cells, HER2 drives tumorigenesis through enhanced signaling and resistance to apoptosis.
HER3 (ERBB3): Although lacking a kinase domain, HER3 forms heterodimers with other ERBB receptors, amplifying signaling pathways that regulate cell proliferation and survival.
HER4 (ERBB4): Involved in various cellular processes, including neurogenesis and heart development, through interaction with specific ligands.

SIGNALING PATHWAYS

The ERBB receptors signal through multiple pathways, including:

Akt Pathway: Involved in cell survival and growth.
MAPK Pathway: Regulates cell proliferation and differentiation.
PI3K Pathway: Plays a role in cellular metabolism and growth.

Autocrine and Paracrine Signaling

ERBB signaling can occur through autocrine mechanisms, where cells produce ligands that activate their own receptors, or paracrine signaling, where ligands affect neighboring cells. This versatility allows for rapid responses to environmental changes and is critical in tumor progression.

ERBB PATHWAY AND CANCER PROGRESSION

The ERBB signaling pathway is implicated in various cancers, particularly breast, lung, and head and neck cancers. Aberrant activation of this pathway, often due to mutations or overexpression of EGFR and HER2, can lead to uncontrolled cell growth and metastasis. Targeted therapies, such as monoclonal antibodies and small molecules that inhibit EGFR and HER2, are commonly used to treat cancers driven by ERBB signaling.

ERBB SIGNALING IN TISSUE REGENERATION AND REPAIR

Beyond cancer, the ERBB pathway is critical in tissue repair and regeneration. It is involved in wound healing and organ regeneration by promoting cell migration, survival, and differentiation. Understanding the molecular mechanisms of ERBB signaling can pave the way for therapeutic strategies to enhance tissue regeneration following injury or in degenerative diseases.

(1) Schramm F et al. EGFR Signaling in Lung Fibrosis. Cells. (2022);11(6):986.

(2) Palumbo C, et al. Recent findings on the impact of ErbB receptors status on prognosis and therapy of head and neck squamous cell carcinoma. Front Med (Lausanne). (2023);10:1066021.

(3) Jacobi N, et al. ErbB Family Signalling: A Paradigm for Oncogene Addiction and Personalized Oncology. Cancers (Basel). (2017);9(4):33.

(4) Ho J, et al. The Role of ErbB Receptors in Infection. Trends Microbiol. (2017); 25(11): 942–952.

ERBB SIGNALING PATHWAY BIOMARKER LIST

Customize your own signaling pathways (SignArrays®) with the factors of your choice!
Simply download and complete our Personalized SignArrays® information file and send it at [email protected] to get started on your project.

You can check the biomarker list included in this pathway, see below:

Species : Homo sapiens (human)

Signaling Pathways	Product ref	Informations
ERBB Signaling Pathway	ERBB1H1	List infos

Species : Mus musculus (mouse)

Signaling Pathways	Product ref	Informations
ERBB Signaling Pathway	ERBB1M1	List infos

Species : Rattus norvegicus (rat)

Signaling Pathways	Product ref	Informations
ERBB Signaling Pathway	*******	List In progress...

Species : Sus Scrofa (Pig)

Signaling Pathways	Product ref	Informations
ERBB Signaling Pathway	*******	List In progress...

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