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Canonical Wnt Signaling Pathway

Canonical Wnt Signaling Pathway

The gene encoding the main signaling molecules of the Wnt signaling pathways (the Wnt proteins) was discovered almost four decades ago by Nüsslein-Volhard and Wieschaus. They identified and originally named the gene "wingless" (wg) after a phenotype discovered during their landmark genetic screen in Drosophila for body pattern defects. At around the same time, another researcher named Harold Varmus found that a murine tumor virus activates the mammalian wg homolog, Int-1, which results in tumor...

Canonical Wnt Signaling Pathway

Canonical Wnt Signaling Pathway

The gene encoding the main signaling molecules of the Wnt signaling pathways (the Wnt proteins) was discovered almost four decades ago by Nüsslein-Volhard and Wieschaus. They identified and originally named the gene "wingless" (wg) after a phenotype discovered during their landmark genetic screen in Drosophila for body pattern defects. At around the same time, another researcher named Harold Varmus found that a murine tumor virus activates the mammalian wg homolog, Int-1, which results in tumor...

Small GTPases - Ras and Rho

Small GTPases - Ras and Rho

Ras and Rho are small monomeric GTPases that act downstream of receptor tyrosine kinase (RTK) and regulate various cellular processes. These GTPases switch between active and inactive states by binding to guanine nucleotides.
Three regulatory proteins control their activity:

The Ras Gene

The Ras Gene

The Ras-gene-encoded proteins are regulators of signaling pathways controlling cell proliferation, differentiation, or cell survival. The Ras-gene family in humans constitutes three primary members—the HRas, NRas, and KRas. These genes code for four functionally distinct yet closely related proteins—the HRas, NRas, KRas4A, and KRas4B. The involvement of mutant Ras genes in human cancer was first discovered in 1982 and is among the most common causes of human tumorigenesis.
Ras is a superfamily...

Non-Canonical Wnt Signaling Pathways

Non-Canonical Wnt Signaling Pathways

Wnt is a zygotic effect gene that is expressed during very early embryonic development. It regulates various processes in animals starting from early development through the adult stage, such as organogenesis in the embryo and maintenance of neuronal and blood stem cells. Wnt proteins can induce a wide variety of intracellular pathways depending upon the specific abilities of different Wnt ligands to form a complex with shared and cognate receptors in the presence of different co-receptors. The...

Non-Canonical Wnt Signaling Pathways

Non-Canonical Wnt Signaling Pathways

Wnt is a zygotic effect gene that is expressed during very early embryonic development. It regulates various processes in animals starting from early development through the adult stage, such as organogenesis in the embryo and maintenance of neuronal and blood stem cells. Wnt proteins can induce a wide variety of intracellular pathways depending upon the specific abilities of different Wnt ligands to form a complex with shared and cognate receptors in the presence of different co-receptors. The...

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Related Experiment Video

Updated: May 18, 2026

The Soft Agar Colony Formation Assay

The Soft Agar Colony Formation Assay

Published on: October 27, 2014

Wnt4 inhibits cell motility induced by oncogenic Ras.

M De Menna¹, V D'Amato, A Ferraro

¹Dipartimento di Biologia e Patologia Cellulare e Molecolare, Università degli Studi di Napoli Federico II, Naples, Italy.

|October 3, 2012

Summary

This summary is machine-generated.

Ras oncogene signaling represses Wnt4, a key protein that inhibits cancer cell motility. This Ras-induced downregulation of Wnt4, mediated by microRNA-24, promotes cancer invasion and metastasis.

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Modeling Paracrine Noncanonical Wnt Signaling In Vitro

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Published on: December 10, 2021

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Last Updated: May 18, 2026

The Soft Agar Colony Formation Assay

The Soft Agar Colony Formation Assay

Published on: October 27, 2014

Modeling Paracrine Noncanonical Wnt Signaling In Vitro

Modeling Paracrine Noncanonical Wnt Signaling In Vitro

Published on: December 10, 2021

Area of Science:

Oncology
Molecular Biology
Cell Biology

Background:

Aberrant cancer cell motility and invasiveness are critical for tumor progression and metastasis.
The molecular pathways governing cancer cell movement are not fully understood.

Purpose of the Study:

To investigate the role of Wnt4 in Ras-induced malignant transformation and cell motility.
To elucidate the regulatory mechanisms controlling Wnt4 expression in cancer.

Main Methods:

Utilized a Ras-induced malignant transformation model.
Analyzed Wnt4 expression in human anaplastic thyroid carcinomas.
Investigated the effects of Wnt4 on actin cytoskeleton reorganization and Rho-GTPase activity.
Identified microRNA-24 (miR-24) as a repressor of Wnt4.

Main Results:

Ras oncogenic signaling represses Wnt4 expression.
Forced Wnt4 expression inhibited Ras-induced cancer cell motility.
Wnt4 downregulation was observed in anaplastic thyroid carcinomas.
Wnt4 modulated actin cytoskeleton organization via non-canonical pathways, affecting Rho-GTPase activation.
miR-24 was identified as a Ras-induced microRNA targeting Wnt4's 3'-untranslated region, leading to its post-transcriptional repression.

Conclusions:

Ras-regulated microRNA-24 circuitry controls Wnt4 expression, impacting cancer cell motility.
Wnt4 acts as a tumor suppressor by inhibiting Ras-driven cell invasion and metastasis.
This study reveals a novel mechanism regulating cancer cell invasiveness.