Related Experiment Video

Updated: Nov 24, 2025

Author Spotlight: Advancements in Cell and Tissue Engineering for Tendon Repair
04:48

Author Spotlight: Advancements in Cell and Tissue Engineering for Tendon Repair

Published on: March 1, 2024

2.2K

Anoikis resistance conferred by tenascin-C-derived peptide TNIIIA2 and its disruption by integrin inactivation

Motomichi Fujita1, Manabu Sasada2, Takuya Iyoda3

  • 1Department of Molecular Patho-Physiology, Faculty of Pharmaceutical Sciences, Tokyo University of Science, 2641 Yamazaki, Noda, Chiba, 278-8510, Japan.

Biochemical and Biophysical Research Communications
|December 28, 2020
PubMed

Insights

Tenascin-C peptide TNIIIA2 activates beta1-integrin, conferring anoikis resistance in glioblastoma multiforme (GBM) cells. Inactivating beta1-integrin with peptide FNIII14 overcomes this resistance, offering a potential therapeutic strategy for GBM.

Area of Science:

  • Oncology
  • Cell Biology
  • Biochemistry

Background:

  • Glioblastoma multiforme (GBM) is an aggressive brain tumor with a poor prognosis, characterized by uncontrolled cell growth and migration.
  • Cancer cells often develop resistance to apoptosis (anoikis) when detached from the extracellular matrix, contributing to tumor progression.
  • Tenascin-C (TNC), highly expressed in GBM, and its derived peptide TNIIIA2, are implicated in GBM aggressiveness via beta1-integrin activation.

Purpose of the Study:

  • To investigate the role of beta1-integrin activation in anoikis resistance in GBM cells.
  • To determine if TNC-derived peptide TNIIIA2 influences anoikis resistance in GBM.
  • To explore the potential of targeting beta1-integrin for overcoming GBM apoptosis resistance.

Main Methods:

  • Utilized the human GBM cell line T98G, which is initially susceptible to anoikis.
  • Treated T98G cells with peptide TNIIIA2 to induce anoikis resistance and peptide FNIII14 to inactivate beta1-integrin.
  • Assessed anchorage-independent survival in suspension culture using various peptides, including TNIIIA2, FNIII14, RGD, and CS-1.

Main Results:

  • Peptide TNIIIA2 treatment rendered anoikis-susceptible T98G cells resistant to anoikis by activating beta1-integrin.
  • The TNIIIA2-induced anoikis resistance was reversed by the addition of peptide FNIII14, which inactivates beta1-integrin.
  • Peptide FNIII14 abrogated anchorage-independent survival of GBM cells, while RGD and CS-1 peptides did not.

Conclusions:

  • GBM cells acquire anoikis resistance through beta1-integrin activation, mediated by TNC-derived peptide TNIIIA2 present in the tumor microenvironment.
  • Inactivation of beta1-integrin presents a promising therapeutic strategy to combat apoptosis resistance in GBM and potentially other cancers.
Keywords:
Anchorage-independent growthAnoikis resistanceGlioblastomaIntegrin activationMatricryptic siteTenascin-C

More Related Videos

2D and 3D Matrices to Study Linear Invadosome Formation and Activity12:25

2D and 3D Matrices to Study Linear Invadosome Formation and Activity

Published on: June 2, 2017

10.3K
Analyzing Cell Surface Adhesion Remodeling in Response to Mechanical Tension Using Magnetic Beads07:55

Analyzing Cell Surface Adhesion Remodeling in Response to Mechanical Tension Using Magnetic Beads

Published on: March 8, 2017

8.7K

Related Concept Videos

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...
3.2K
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...
4.6K
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,...
4.8K
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...
3.2K
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,...
2.6K
Role Of Notch Signalling In Intestinal Stem Cell Renewal01:12

Role Of Notch Signalling In Intestinal Stem Cell Renewal

Notch signaling was first discovered in Drosophila melanogaster, where it is involved in cell lineage differentiation. Notch signaling regulates the maintenance and differentiation of intestinal stem cells or ISCs by controlling the expression of atonal homolog 1 or Atoh1. Atoh1 directs cells to differentiate into secretory cells.
Direct cell-to-cell contact is needed for the activation of Notch signaling. The signal is initiated when a notch ligand binds to a receptor on an adjacent cell, also...
2.3K