Related Experiment Video
Updated: Jan 21, 2026
Intracarotid Cancer Cell Injection to Produce Mouse Models of Brain Metastasis
Published on: February 8, 2017
The Structural Function of Nestin in Cell Body Softening is Correlated with Cancer Cell Metastasis
Ayana Yamagishi1, Moe Susaki2, Yuta Takano2
1Biomedical Research Institute, National Institute of Advanced Industrial Science and Technology (AIST), Central 5 1-1-1 Higashi, Tsukuba, Ibaraki, 305-8565, Japan.
Abstract:
Intermediate filaments play significant roles in governing cell stiffness and invasive ability. Nestin is a type VI intermediate filament protein that is highly expressed in several high-metastatic cancer cells. Although inhibition of nestin expression was shown to reduce the metastatic capacity of tumor cells, the relationship between this protein and the mechanism of cancer cell metastasis remains unclear. Here, we show that nestin softens the cell body of the highly metastatic mouse breast cancer cell line FP10SC2, thereby enhancing the metastasis capacity. Proximity ligation assay demonstrated increased binding between actin and vimentin in nestin knockout cells. Because nestin copolymerizes with vimentin and nestin has an extremely long tail domain in its C-terminal region, we hypothesized that the tail domain functions as a steric inhibitor of the vimentin-actin interaction and suppresses association of vimentin filaments with the cortical actin cytoskeleton, leading to reduced cell stiffness. To demonstrate this function, we mechanically pulled vimentin filaments in living cells using a nanoneedle modified with vimentin-specific antibodies under manipulation by atomic force microscopy (AFM). The tensile test revealed that mobility of vimentin filaments was increased by nestin expression in FP10SC2 cells.
Insights
Nestin, a protein found in metastatic cancer cells, softens cells by altering interactions between actin and vimentin. This softening enhances cancer cell metastasis, revealing a new mechanism for tumor cell invasion.
Area of Science:
- Cell Biology
- Biophysics
- Cancer Research
Background:
- Intermediate filaments regulate cell mechanics and invasion.
- Nestin, a type VI intermediate filament protein, is upregulated in highly metastatic cancers.
- The precise role of nestin in cancer cell metastasis is not fully understood.
Purpose of the Study:
- To investigate the role of nestin in regulating cell stiffness and metastasis.
- To elucidate the molecular mechanism by which nestin influences cancer cell invasion.
Main Methods:
- Utilized a highly metastatic mouse breast cancer cell line (FP10SC2).
- Generated nestin knockout cells to assess its function.
- Employed proximity ligation assay to study protein interactions.
- Used atomic force microscopy (AFM) with a nanoneedle to perform mechanical tensile tests on vimentin filaments.
Main Results:
- Nestin expression softens the cell body, enhancing metastatic capacity.
- Nestin knockout cells showed increased binding between actin and vimentin.
- Mechanical pulling of vimentin filaments revealed increased mobility in nestin-expressing cells.
- Hypothesized nestin's C-terminal tail domain inhibits vimentin-actin interaction, reducing cell stiffness.
Conclusions:
- Nestin softens cancer cells, promoting metastasis by modulating vimentin-actin interactions.
- The nestin tail domain may act as a steric inhibitor, suppressing vimentin filament association with the actin cytoskeleton.
- Findings provide novel insights into the biophysical mechanisms of cancer cell invasion.
Related Concept Videos
01:56Structural Protein Function
Collagen, the most abundant protein in mammals, is found throughout the body. In connective tissue, such as skin, ligaments, and tendons, it provides tensile strength and elasticity. In bones and teeth, it mineralizes to...
01:56Structural Protein Function
01:58Fruit Development, Structure, and Function
01:23Neurons: The Cell Body and the Dendrites
01:18Structural Organization of the Human Body: An Overview
To study the chemical level of organization, scientists consider the simplest building blocks of matter: subatomic particles, atoms, and molecules. All matter in the universe is composed of one or more unique pure substances called elements, familiar examples of...
02:20Correlations