Introduction To Wnt/Β-Catenin Signalling

Introduction :
The Wnt/β-catenin signalling pathway is essential for embryonic development and adult tissue
homeostasis. Dysregulation of this pathway is linked to various diseases, making it a promising target
for therapeutic interventions. The review discusses non-tumour diseases like hair loss, wound healing,
and neurodegenerative diseases, as well as tumour diseases such as cancer stem cells and metastasis.
The clinical application of the Wnt/β-catenin pathway in disease diagnosis and treatment is also
explored
INTRODUCTION TO WNT/Β-CATENIN SIGNALLING
The Wnt/β-catenin signalling pathway, originating from the Wnt gene, is crucial for embryonic
development and tissue homeostasis. Aberrant regulation of this pathway is associated with various
diseases, highlighting its potential as a therapeutic target. The pathway's role in both non-tumour
diseases and tumour diseases, including cancer stem cells and metastasis, is extensively reviewed in the
context of diagnosis and treatment
fig1
Figure 1 likely illustrates the Wnt/β-catenin signalling pathway, depicting the key molecular components
and interactions involved in the pathway's activation and regulation. The diagram may show how Wnt
ligands bind to receptors such as Frizzled (FZD) and LRP5/6, leading to the stabilization of β-catenin and
its translocation to the nucleus. This translocated β-catenin then interacts with transcription factors like
TCF/LEF to regulate the expression of target genes. Additionally, the figure may highlight the role of
regulatory proteins like GSK-3β, APC, and CK-1α in controlling β-catenin levels through phosphorylation
and degradation processes. Overall, Figure 1 likely provides a visual representation of the intricate
molecular mechanisms underlying Wnt/β-catenin signalling and its impact on cellular functions.
Figure 2 likely provides a comprehensive overview of the inhibitors and activators of the
Wnt/β-catenin signalling pathway. Here is an explanation based on the description provided:
A. Inhibitors of the Wnt/β-catenin Signalling Pathway:
1. sFRPs, WIF, Tiki, and Notum: These inhibitors are located outside the plasma membrane and function
by interacting with Wnts to inhibit Wnt signal transduction.
2. FZD, LRP5/6, RNF43/ZNRF3, Krem-1/2, ROR, RYK, and glypican: These components are located on the
plasma membrane. RNF43/ZNRF3 binds to the FZD receptor complex, leading to its ubiquitination and
endocytosis. ROR, RYK, and glypican bind to Wnts to inhibit Wnt signal transduction. DKK1/3/4 binds to
LRP5/6 or forms a complex with Krem-1/2 to induce endocytosis. Groucho, located in the nucleus,
inhibits the transcription of target genes by binding to LEF.
B. Activators of the Wnt/β-catenin Signalling Pathway:
1. R-spondin and Norrin: Located outside the plasma membrane, these molecules play a role in
activating the pathway.
2. FZD, LRP5/6, RNF43/ZNRF3, and LGR4/5: These components are located on the plasma membrane.
The β-catenin destruction complex (comprising axin, APC, GSK-3β, CK-1α, and β-catenin) and PP2A are
located in the cytoplasm. TCF/LEF is located in the nucleus. Association of LGR4/5 and RNF43/ZNRF3
with R-spondin induces membrane retention of FZD. Norrin acts as a mimic of Wnts to activate signal
transduction. PP2A dephosphorylates β-catenin, promoting its accumulation in the cytoplasm. β-catenin
then enters the nucleus and interacts with TCF/LEF to initiate the transcription of target genes.
This figure likely provides a visual representation of the various molecules and their locations within the
cellular environment, highlighting their roles as inhibitors or activators in the intricate Wnt/β-catenin
signalling pathway.
The introduction to Wnt/β-catenin signalling likely provides a foundational overview of this critical
cellular pathway. Here is a general explanation based on common themes found in introductions to
Wnt/β-catenin signalling:
The Wnt/β-catenin signalling pathway is a fundamental cellular pathway that plays a crucial role in
various biological processes, including embryonic development, tissue homeostasis, and disease
pathogenesis. The pathway is initiated by Wnt ligands, which bind to cell surface receptors such as
Frizzled (FZD) and lipoprotein receptor-related proteins (LRP5/6), leading to the activation of
downstream signalling cascades.
Upon Wnt ligand binding, the destruction complex, consisting of proteins like axin, APC, GSK-3β, and
CK-1α, is inhibited, resulting in the stabilization and accumulation of β-catenin in the cytoplasm.
Accumulated β-catenin translocates into the nucleus, where it interacts with transcription factors of the
T-cell factor/lymphoid enhancer factor (TCF/LEF) family to regulate the expression of target genes
involved in cell proliferation, differentiation, and survival.

The precise regulation of Wnt/β-catenin signalling is essential for normal cellular function, and
dysregulation of this pathway has been implicated in various diseases, including cancer,
neurodegenerative disorders, and developmental abnormalities. Therefore, understanding the
mechanisms underlying Wnt/β-catenin signalling is crucial for developing targeted therapeutic
interventions for diseases associated with pathway dysregulation.
Overall, the introduction to Wnt/β-catenin signalling likely sets the stage for a detailed exploration of
the molecular mechanisms, biological functions, and therapeutic implications of this critical signalling
pathway in cellular physiology and disease.

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Introduction :

B. Activators of the Wnt/β-catenin Signalling Pathway:

downstream signalling cascades.

involved in cell proliferation, differentiation, and survival.

neurodegenerative disorders, and developmental abnormalities. Therefore, understanding the

mechanisms underlying Wnt/β-catenin signalling is crucial for developing targeted therapeutic

interventions for diseases associated with pathway dysregulation.

pathway in cellular physiology and disease.

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