Related Experiment Video

Updated: Jul 14, 2026

Studying TGF-β Signaling and TGF-β-induced Epithelial-to-mesenchymal Transition in Breast Cancer and Normal Cells
06:54

Studying TGF-β Signaling and TGF-β-induced Epithelial-to-mesenchymal Transition in Breast Cancer and Normal Cells

Published on: October 27, 2020

Smad4-independent TGF-beta signaling in tumor cell migration

Klaudia Giehl1, Yukiko Imamichi, Andre Menke

  • 1Institute of Pharmacology and Toxicology, University of Ulm Medical Center, Ulm, Germany. klaudia.giehl@uni-ulm.de

Cells, Tissues, Organs
|June 26, 2007
PubMed

Insights

Transforming growth factor-beta (TGF-beta) promotes cancer cell migration via Smad4-independent pathways. Activated MAP kinases, ERK and JNK, are key players in this TGF-beta-induced tumor invasiveness.

Area of Science:

  • Cell Biology
  • Molecular Oncology
  • Cancer Research

Background:

  • Transforming growth factor-beta (TGF-beta) regulates diverse cellular functions, including epithelial cell proliferation and differentiation.
  • While TGF-beta inhibits epithelial cell growth via the Smad pathway, its role in promoting epithelial-mesenchymal transition, invasiveness, and metastasis in tumors is less understood.
  • Tumorigenic activity induced by TGF-beta involves signaling pathways beyond Smads, including Rho-GTPases and MAP kinases.

Purpose of the Study:

  • To review the molecular mechanisms underlying TGF-beta-induced epithelial tumor invasiveness and metastasis.
  • To highlight the role of MAP kinases, specifically ERK and JNK, in TGF-beta-mediated cell migration.
  • To discuss the Smad4-independent signaling pathways involved in TGF-beta's pro-tumorigenic effects.

Main Methods:

  • Review of recent scientific literature and experimental findings.
  • Analysis of signaling pathways, including Smad, Rho-GTPases, and MAP kinases (ERK, JNK).
  • Focus on Smad4-independent signal transduction in epithelial cells, particularly breast carcinoma cells.

Main Results:

  • Activation of extracellular signal-regulated kinases (ERK) 1/2 and c-jun N-terminal kinase (JNK) are critical for TGF-beta-induced, Smad4-independent signal transduction.
  • Activated ERK and JNK associate with focal complexes, mediating TGF-beta-induced cell migration in breast carcinoma cells.
  • These findings suggest a significant role for MAP kinases in TGF-beta's promotion of tumor invasiveness.

Conclusions:

  • TGF-beta-induced tumor cell migration and metastasis involve Smad4-independent signaling pathways.
  • MAP kinases (ERK and JNK) are crucial mediators of TGF-beta's pro-migratory effects in epithelial tumors.
  • Understanding these pathways offers potential therapeutic targets for inhibiting cancer progression.

More Related Videos

Live Cell Imaging of the TGF- β/Smad3 Signaling Pathway In Vitro and In Vivo Using an Adenovirus Reporter System11:06

Live Cell Imaging of the TGF- β/Smad3 Signaling Pathway In Vitro and In Vivo Using an Adenovirus Reporter System

Published on: July 30, 2018

Spheroid Assay to Measure TGF-β-induced Invasion09:18

Spheroid Assay to Measure TGF-β-induced Invasion

Published on: November 16, 2011

Related Concept Videos

TGF - β Signaling Pathway01:16

TGF - β Signaling Pathway

The TGF-β signaling pathway regulates cell growth, differentiation, adhesion, motility, and development. TGF-β ligands that induce TGF-β signaling are synthesized in their latent form. Several proteases or cell surface receptors such as integrins act upon the latent form, releasing the active ligand. There are three types of mammalian TGF-βs: (TGF-β1, TGF-β2, and TGF-β3) that bind as homodimers or heterodimers to TGF-β receptors. The TGF-β receptors are of three kinds RI, RII, and RIII. The RI...
Intracellular Signaling Affects Focal Adhesions01:17

Intracellular Signaling Affects Focal Adhesions

Integrins act both as extracellular input receivers and as intracellular processing activators. As their name suggests, integrins are entirely integrated into the membrane structure. Their hydrophobic membrane-spanning regions interact with the phospholipid bilayer's hydrophobic region. These membrane receptors provide extracellular attachment sites for effectors like hormones and growth factors. They activate intracellular response cascades when their effectors are bound and active.
Some...
Cell Migration01:09

Cell Migration

Cell migration, the process by which cells move from one location to another, is essential for the proper development and viability of organisms throughout their life. When cells are not able to migrate properly to their ordained locations, various disorders may occur. For example, disruption in cell migration causes chronic inflammatory diseases such as arthritis.
Cell Migration01:19

Cell Migration

Cell migration is a process by which the cells move from one location to another, playing an essential role in embryological development, repair and regeneration, immune response, and metastasis. Cells migrate in response to chemical or mechanical signals generated by specific organs or tissues. The overall mechanism includes three steps - polarization, protrusion, and release. Polarization involves the formation of a distinct cell front and rear, which determines the direction of movement.
Cancer Cell Migration through Invadopodia01:35

Cancer Cell Migration through Invadopodia

Invadosome is a broad category of cell surface structures with proteolytic activity that  degrades the extracellular matrix (ECM). Invadosomes are present in normal cell types, including macrophages, endothelial cells, and neurons, as well as tumor cells. Although the macrophage podosomes and tumor cell invadopodia are classified as invadosomes, they have different structures, molecular pathways, and functions. Podosomes are short structures that last for a few minutes. However, invadopodia can...
The Tumor Microenvironment02:17

The Tumor Microenvironment

Every normal cell or tissue is embedded in a complex local environment called stroma, consisting of different cell types, a basal membrane, and blood vessels. As normal cells mutate and develop into cancer cells, their local environment also changes to allow cancer progression. The tumor microenvironment (TME) consists of a complex cellular matrix of stromal cells and the developing tumor. The cross-talk between cancer cells and surrounding stromal cells is critical to disrupt normal tissue...