Related Experiment Video
Updated: Mar 7, 2026

Enhancing the Engraftment of Human Induced Pluripotent Stem Cell-derived Cardiomyocytes via a Transient Inhibition of Rho Kinase Activity
Published on: July 10, 2019
Blockade of Rho-associated protein kinase (ROCK) inhibits the contractility and invasion potential of cancer stem
Srisathya Srinivasan1, Vandhana Ashok1, Sagarajit Mohanty1
1Department of Biosciences & Bioengineering, Indian Institute of Technology Bombay (IIT Bombay), Mumbai, Maharashtra, India.
Abstract:
Recent studies have implicated the roles of cancer stem like cells (CSCs) in cancer metastasis. However, very limited knowledge exists at the molecular and cellular level to target CSCs for prevention of cancer metastasis. In this study, we examined the roles of contractile dynamics of CSCs in cell invasion and delineated the underlying molecular mechanisms of their distinct cell invasion potential. Using de-adhesion assay and atomic force microscopy, we show that CSCs derived from melanoma and breast cancer cell lines exhibit increased contractility compared to non-CSCs across all tumor types. In addition, CSCs possess increased ECM remodeling capacity as quantified by collagen degradation assay. More importantly, pharmacological blockade of Rho-associated protein kinase completely abolished the contractility and collagen degradation capacity of both CSCs and non-CSCs. In conclusion, our study demonstrates the importance of cell contractility in regulating invasiveness of CSCs and suggests that pharmacological targeting of ROCK pathway represents a novel strategy for targeting both CSCs and bulk population for the treatment of cancer metastasis.
Insights
Cancer stem-like cells (CSCs) show increased contractility and invasion potential, driving metastasis. Targeting the ROCK pathway offers a novel strategy to inhibit CSC invasiveness and treat cancer metastasis.
Area of Science:
- Oncology
- Cell Biology
- Biophysics
Background:
- Cancer stem-like cells (CSCs) are implicated in cancer metastasis.
- Molecular and cellular mechanisms underlying CSC invasiveness remain poorly understood.
Purpose of the Study:
- To investigate the role of contractile dynamics in CSC invasion.
- To identify molecular mechanisms regulating CSC invasiveness.
Main Methods:
- De-adhesion assays and atomic force microscopy to measure cell contractility.
- Collagen degradation assays to assess extracellular matrix (ECM) remodeling.
- Pharmacological inhibition of Rho-associated protein kinase (ROCK).
Main Results:
- CSCs exhibit significantly higher contractility and ECM remodeling capacity than non-CSCs.
- Pharmacological blockade of ROCK completely eliminated contractility and collagen degradation in both CSCs and non-CSCs.
- ROCK pathway inhibition normalized CSC and non-CSC invasiveness.
Conclusions:
- Cell contractility is crucial for regulating CSC invasiveness.
- Targeting the ROCK pathway is a promising therapeutic strategy for inhibiting cancer metastasis by affecting both CSCs and bulk tumor cells.
Related Concept Videos
Small GTPases - Ras and Rho
Three regulatory proteins control their activity:
mTOR Signaling and Cancer Progression
The mTOR pathway or the...
Inhibition of Cdk Activity
PI3K/mTOR/AKT Signaling Pathway
Cell Polarization by Rho Proteins
The Ras Gene
Ras is a...

