Related Experiment Video

Updated: Aug 10, 2026

Static Adhesion Assay for the Study of Integrin Activation in T Lymphocytes
09:14

Static Adhesion Assay for the Study of Integrin Activation in T Lymphocytes

Published on: June 13, 2014

TGFbeta1 signaling via alphaVbeta6 integrin

Martin P Kracklauer1, Christian Schmidt, Guido M Sclabas

  • 1Section of Molecular Cell and Developmental Biology, Institute for Cellular and Molecular Biology, The University of Texas at Austin, 1 University Station, A4800, 78712, Austin, TX, USA. mordechai30@hotmail.com

Molecular Cancer
|August 26, 2003
PubMed
Abstract

Insights

Transforming growth factor beta1 (TGFbeta1) signals through alphaVbeta6 integrin, independent of the SMAD pathway. This alternate pathway inhibits carcinoma cell growth, even in SMAD4-deficient cells, revealing a new target for cancer therapy.

Area of Science:

  • Cell Biology
  • Molecular Oncology
  • Cancer Signaling

Background:

  • Transforming growth factor beta1 (TGFbeta1) inhibits epithelial cell growth and maintains tissue homeostasis.
  • Carcinoma cells often show reduced sensitivity to TGFbeta1, implicating it in cancer development.
  • The tumor suppressor gene DPC4/SMAD4 is crucial for TGFbeta1 growth inhibition, but SMAD4-independent pathways exist.

Purpose of the Study:

  • To investigate the SMAD4-independent TGFbeta1 signaling pathway in carcinoma cells.
  • To identify novel ligands and mediators of TGFbeta1-induced growth inhibition.

Main Methods:

  • Investigated TGFbeta1 binding to integrins.
  • Analyzed signaling protein activation in response to TGFbeta1.
  • Assessed the role of alphaVbeta6 integrin in TGFbeta1 signaling.
  • Measured cell cycle inhibitor expression (p21/WAF1, p27) and cell growth.

Main Results:

  • Mature TGFbeta1 directly binds to integrin alphaVbeta6, independent of the RGD motif.
  • TGFbeta1-alphaVbeta6 interaction activates signaling proteins in TGFbeta1-sensitive carcinoma cells.
  • This interaction upregulates cell cycle inhibitors p21/WAF1 and p27, inhibiting growth in both SMAD4-deleted and SMAD4-wildtype cells.

Conclusions:

  • A SMAD4-independent TGFbeta1 signaling pathway involving alphaVbeta6 integrin exists.
  • This pathway utilizes the Ras/MAP kinase pathway and does not require an RGD motif.
  • Both SMAD-dependent and alphaVbeta6-mediated pathways are necessary for a complete TGFbeta1 signal.

More Related Videos

Studying TGF-β Signaling and TGF-β-induced Epithelial-to-mesenchymal Transition in Breast Cancer and Normal Cells06:54

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

Published on: October 27, 2020

Tension Gauge Tether Probes for Quantifying Growth Factor Mediated Integrin Mechanics and Adhesion09:56

Tension Gauge Tether Probes for Quantifying Growth Factor Mediated Integrin Mechanics and Adhesion

Published on: February 11, 2022

Related Concept Videos

Assembly of Signaling Complexes01:30

Assembly of Signaling Complexes

Multiprotein signaling complexes are formed in a dynamic process involving protein-protein interactions at the cytoplasmic domain of transmembrane receptors or enzymatic and non-enzymatic proteins associated with the receptor. These complexes ensure the activation and propagation of intracellular signals that regulate cell functions.
Interaction domains in cell signaling
Interaction domains recognize exposed features of their binding partners containing post-translationally modified sequences,...
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...
Activation and Inactivation of G Proteins01:22

Activation and Inactivation of G Proteins

Heterotrimeric G proteins are guanine nucleotide-binding proteins. As the name suggests, heterotrimeric G proteins are composed of three subunits: alpha, beta, and gamma. They remain GDP-bound or GTP-bound inside the cells and switch between inactive/active states. The Gα subunit possesses the nucleotide-binding pocket that binds guanine nucleotides and switches between GDP or GTP-bound states. In contrast, the Gꞵ and Gγ subunits are always bound together with high affinity and are together...
Integrins01:10

Integrins

Animal and protozoan cells do not have cell walls to help maintain shape and provide structural stability. Instead, these eukaryotic cells secrete a sticky mass of carbohydrates and proteins into the spaces between adjacent cells. This network of proteins and molecules is called an extracellular matrix or ECM.
Some ECM proteins assemble into a basement membrane to which the remaining components adhere. Proteoglycans typically form the bulk of the ECM while fibrous proteins, like collagen,...
Activation of Integrins01:15

Activation of Integrins

Integrins bind ligands and transmit information from outside the cell to inside or vice-versa through an "outside-in signaling" or "inside-out signaling."
In "outside-in signaling," external factors in the extracellular space bind to exposed ligand binding sites on integrins. This causes the inactive protein to undergo a conformational change to become active. Integrins are often clustered on the cell membrane. Repetitive and regularly spaced ligand binding events provide an effective stimulus.
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...