NOTCH SIGNALING PATHWAY: A MASTER REGULATOR OF CELL FATE

The Notch signaling pathway is a fundamental mechanism in cellular communication that regulates various processes, including cell differentiation, proliferation, and apoptosis. It plays a critical role in the development of numerous tissues and organs, such as the nervous system, blood vessels, and immune cells.

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Intracellular Notch signaling cascade.

ACTIVATION AND KEY COMPONENTS OF NOTCH SIGNALING PATHWAY

Notch signaling is activated when the Notch receptor on the cell surface binds to a ligand (Delta or Jagged) on an adjacent cell. This interaction triggers proteolytic cleavage of the receptor, releasing the Notch intracellular domain (NICD), which translocates to the nucleus to initiate transcription of target genes.

Key Components:

Notch Receptors: Four Notch receptors (Notch1-4) are present in mammals and mediate the signal transduction process.
Notch Ligands: The ligands Delta and Jagged, expressed on adjacent cells, bind to the Notch receptor to activate the pathway.
NICD (Notch Intracellular Domain): After receptor activation, NICD is released and enters the nucleus to regulate gene expression.
CSL (CBF1/Su(H)/Lag-1): The transcription factor that forms a complex with NICD to activate downstream genes.

NOTCH SIGNALING IN DEVELOPMENT AND DISEASES

The Notch pathway is essential for proper tissue and organ development, including:

Neurogenesis: Regulates the differentiation of neural stem cells.
Hematopoiesis: Controls the development of blood cells.
Vascular Development: Influences the formation of blood vessels.
Immune System Regulation: Plays a role in the development and function of immune cells.

Dysregulation of Notch pathway is associated with various diseases, such as:

Cancer: Aberrant activation or suppression of Notch pathway can contribute to tumor progression and metastasis.
Cardiovascular Disease: Altered Notch pathway disrupts blood vessel formation and function.
Neurodegenerative Disorders: Impaired Notch pathway is linked to conditions like Alzheimer's disease.

CROSSTALK BETWEEN NOTCH AND OTHER PATHWAYS

Notch pathway interacts with various cellular pathways, creating a network of regulation that influences diverse cellular processes. For example:

Notch and Wnt/β-Catenin: These pathways coordinate during tissue repair and stem cell differentiation.
Notch and Hedgehog: Together, they regulate organogenesis and maintain tissue homeostasis.
Notch and PI3K-Akt: This interaction modulates cell survival and proliferation in response to stress.

These interactions highlight the complexity of Notch signaling and its impact on health and disease. Understanding these relationships is crucial for unraveling the broader implications of the pathway.

NOTCH SIGNALING IN CANCER PROGRESSION

Notch pathway plays a dual role in cancer, acting as both an oncogene and a tumor suppressor depending on the context.

As an Oncogene: Overactivation of Notch pathway drives tumor growth in cancers such as leukemia, breast cancer, and pancreatic cancer.
As a Tumor Suppressor: In other contexts, Notch pathway prevents uncontrolled cell division and promotes differentiation, suppressing tumor formation.

This duality makes the pathway a promising therapeutic target. Researchers are investigating drugs that modulate Notch signaling, aiming to treat cancers more effectively.

(1) Luo Z et al. Notch Signaling in Osteogenesis, Osteoclastogenesis, and Angiogenesis. Am J Pathol. (2019);189(8):1495-1500.

(2) Han J & al. Regulation of Adipogenesis Through Differential Modulation of ROS and Kinase Signaling Pathways by 3,4'-Dihydroxyflavone Treatment. J Cell Biochem. (2017);118(5):1065-1077.

(3) Zhang Z1 & Scherer PE. Adipose tissue: The dysfunctional adipocyte - a cancer cell's best friend. Nat Rev Endocrinol. (2018);14(3):132-134.

(4) Duong MN & al. The fat and the bad: Mature adipocytes, key actors in tumor progression and resistance. Oncotarget. (2017).

(5) Choi J & al. Adipocyte biology in breast cancer: From silent bystander to active facilitator. Prog Lipid Res. (2018);(69):11-20.

NOTCH 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
Notch Signaling Pathway	NOCH1H1	List infos

Species : Mus musculus (mouse)

Signaling Pathways	Product ref	Informations
Notch Signaling Pathway	NOCH1M1	List infos

Species : Rattus norvegicus (rat)

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

Species : Sus Scrofa (Pig)

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

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