Related Experiment Video

Updated: May 25, 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

Matrix rigidity regulates a switch between TGF-β1-induced apoptosis and epithelial-mesenchymal transition

Jennifer L Leight1, Michele A Wozniak, Sophia Chen

  • 1Department of Bioengineering, University of Pennsylvania, Philadelphia, PA 19104, USA.

Molecular Biology of the Cell
|January 13, 2012
PubMed

Insights

Tissue stiffness regulates transforming growth factor-β (TGF-β) signaling, switching its function from tumor suppression to promoting cancer progression. This study reveals how matrix rigidity influences TGF-β

Area of Science:

  • Cell Biology
  • Biophysics
  • Cancer Research

Background:

  • The transforming growth factor-β (TGF-β) pathway plays a dual role in cancer, acting as a tumor suppressor early on and a promoter later.
  • Tumor progression is associated with increased tissue stiffness, but its influence on TGF-β signaling is not well understood.

Purpose of the Study:

  • To investigate whether changes in matrix rigidity can regulate the functional outcomes of TGF-β signaling.
  • To elucidate the molecular mechanisms underlying the interplay between matrix rigidity and TGF-β responses.

Main Methods:

  • Culturing normal murine mammary gland cells and Madin-Darby canine kidney epithelial cells on polyacrylamide gels of varying rigidity.
  • Treating cells with TGF-β1 and assessing responses such as apoptosis and epithelial-mesenchymal transition (EMT).
  • Analyzing Smad and PI3K/Akt signaling pathways, and utilizing genetic and pharmacologic manipulations.

Main Results:

  • Matrix rigidity significantly altered the cellular response to TGF-β1.
  • Decreased rigidity promoted TGF-β1-induced apoptosis, while increased rigidity induced EMT.
  • TGF-β1's effects were mediated by the PI3K/Akt pathway, not Smad signaling, with rigidity acting as a key regulator.

Conclusions:

  • Matrix rigidity acts as a critical regulator, switching TGF-β1's cellular functions between apoptosis induction and EMT.
  • This finding highlights a novel mechanism by which the biophysical properties of the tumor microenvironment influence cancer progression.
  • Understanding this interplay offers new insights into therapeutic strategies targeting TGF-β signaling in cancer.

More Related Videos

Development of an In Vitro Assay to Evaluate Contractile Function of Mesenchymal Cells that Underwent Epithelial-Mesenchymal Transition06:02

Development of an In Vitro Assay to Evaluate Contractile Function of Mesenchymal Cells that Underwent Epithelial-Mesenchymal Transition

Published on: June 10, 2016

Induction and Analysis of Epithelial to Mesenchymal Transition10:37

Induction and Analysis of Epithelial to Mesenchymal Transition

Published on: August 27, 2013

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...
Receptor Downregulation in MVBs01:15

Receptor Downregulation in MVBs

Multivesicular bodies (MVBs) are mature endosomes that sort ubiquitinated proteins and then fuse with lysosomes to degrade the sorted proteins. Epidermal growth factor (EGF) and its receptor (EGFR) form a complex that can be internalized through endocytosis, sorted into an MVB, and later degraded.
The EGFR can initiate signaling pathways that  lead to cell proliferation, migration, and differentiation. Overexpression of EGFR  stimulates cells to proliferate. Excessive  EGFR activation may...
Cell-matrix's Response to Mechanical Forces01:13

Cell-matrix's Response to Mechanical Forces

In animal cells, the extracellular matrix allows cells within tissues to withstand external stresses and transmits signals from the outside of the cell to the inside. The extracellular matrix is extensive, and its composition varies between different types of tissues. For example, the reticular fibers and ground substance make up the ECM in loose connective tissue, while collagen and bone minerals make up the ECM of bone tissue. 
Anchoring junctions mechanically attach a cell to the...
Cadherins in Tissue Organization01:19

Cadherins in Tissue Organization

The cadherins are a superfamily of cell adhesion molecules comprising over 180 variants, with specific tissues expressing a particular combination of cadherin types. Cadherins generally exhibit homophilic binding; i.e., cadherins on one cell bind to cadherins of the same or closely related type on another cell. Thus, cells of the same type have a specific affinity to bind to each other and sort themselves into clusters to form tissues.
Cell Sorting During Development
Cell sorting plays an...
Role of Matrix Metalloproteases in Degradation of ECM01:23

Role of Matrix Metalloproteases in Degradation of ECM

Matrix metalloproteases (MMPs) are enzymes involved in the hydrolysis of proteins and glycoproteins of the extracellular matrix. MMPs are essential for the migration and proliferation of cells through the dense matrix network, throughout embryonic development, and throughout morphogenesis. The first MMP activity discovered was a collagenase in a tadpole's tail undergoing metamorphosis. The active collagen deposition and modifications lead to the morphogenesis of tadpoles into the adult body.
A...
Tension Response at Adherens Junctions01:26

Tension Response at Adherens Junctions

The adherens junctions that anchor cells together are multi-protein complexes that dynamically adapt to mechanical stimuli such as tensile forces and shear stress. Mechanosensory proteins in these junctions can sense such mechanical stimuli and undergo a shift in their conformation, resulting in an altered function — a process called mechanotransduction.
α-Catenin as a Mechanosensory Protein
The α-catenin of adherens junctions is an allosteric protein with three VH (vinculin homology) domains...