title: Blockade of Rho-associated protein kinase (ROCK) inhibits the contractility and invasion potential of cancer stem like cells.
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.
authors.affiliation: Department of Biosciences & Bioengineering, Indian Institute of Technology Bombay (IIT Bombay), Mumbai, Maharashtra, India.
authors.forename: Srisathya
authors.initials: S
authors.lastname: Srinivasan
authors.affiliation: Department of Biosciences & Bioengineering, Indian Institute of Technology Bombay (IIT Bombay), Mumbai, Maharashtra, India.
authors.forename: Vandhana
authors.initials: V
authors.lastname: Ashok
authors.affiliation: Department of Biosciences & Bioengineering, Indian Institute of Technology Bombay (IIT Bombay), Mumbai, Maharashtra, India.
authors.forename: Sagarajit
authors.initials: S
authors.lastname: Mohanty
authors.affiliation: Department of Biosciences & Bioengineering, Indian Institute of Technology Bombay (IIT Bombay), Mumbai, Maharashtra, India.
authors.forename: Alakesh
authors.initials: A
authors.lastname: Das
authors.affiliation: Department of Biosciences & Bioengineering, Indian Institute of Technology Bombay (IIT Bombay), Mumbai, Maharashtra, India.
authors.forename: Sreya
authors.initials: S
authors.lastname: Das
authors.affiliation: Department of Biosciences & Bioengineering, Indian Institute of Technology Bombay (IIT Bombay), Mumbai, Maharashtra, India.
authors.forename: Sushant
authors.initials: S
authors.lastname: Kumar
authors.affiliation: Department of Biosciences & Bioengineering, Indian Institute of Technology Bombay (IIT Bombay), Mumbai, Maharashtra, India.
authors.forename: Shamik
authors.initials: S
authors.lastname: Sen
authors.affiliation: Department of Biosciences & Bioengineering, Indian Institute of Technology Bombay (IIT Bombay), Mumbai, Maharashtra, India.
authors.forename: Rahul
authors.initials: R
authors.lastname: Purwar
mesh_terms: D045744:Cell Line, Tumor; D002465:Cell Movement / Q000502:physiology; D005434:Flow Cytometry; D006801:Humans; D018625:Microscopy, Atomic Force; D009361:Neoplasm Invasiveness / Q000473:pathology*; D014411:Neoplastic Stem Cells / Q000201:enzymology* / Q000473:pathology*; D060888:Real-Time Polymerase Chain Reaction; D054460:rho-Associated Kinases / Q000378:metabolism*
chemical_list: D054460:rho-Associated Kinases
keywords: cancer stem cells; cell contractility; invasion; metastasis; rock pathway