Blockade of Rho-associated protein kinase (ROCK) inhibits the contractility and invasion potential of cancer stem like cells

Abstract

// Srisathya Srinivasan 1, * , Vandhana Ashok 1, * , Sagarajit Mohanty 1 , Alakesh Das 1 , Sreya Das 1 , Sushant Kumar 1 , Shamik Sen 1 , Rahul Purwar 1 1 Department of Biosciences & Bioengineering, Indian Institute of Technology Bombay (IIT Bombay), Mumbai, Maharashtra, India * These authors have contributed equally to this work Correspondence to: Rahul Purwar, email: [e-mail] Shamik Sen, email: [e-mail] Keywords: ROCK pathway, cancer stem cells, cell contractility, invasion, metastasis Received: October 15, 2016     Accepted: January 17, 2017     Published: February 10, 2017 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.