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.

Oncotarget
|February 16, 2017
PubMed

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.

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