Blockade of Rho-associated protein kinase (ROCK) inhibits the contractility and invasion potential of cancer stem like cells
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Srisathya Srinivasan1,*, Vandhana Ashok1,*, Sagarajit Mohanty1, Alakesh Das1, Sreya Das1, Sushant Kumar1, Shamik Sen1, Rahul Purwar1
1Department of Biosciences & Bioengineering, Indian Institute of Technology Bombay (IIT Bombay), Mumbai, Maharashtra, India
*These authors have contributed equally to this work
Rahul Purwar, email: [email protected]
Shamik Sen, email: [email protected]
Keywords: ROCK pathway, cancer stem cells, cell contractility, invasion, metastasis
Received: October 15, 2016 Accepted: January 17, 2017 Published: February 10, 2017
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.
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