PMID: 25749040Mar 10, 2015Paper

ROCK inhibition promotes microtentacles that enhance reattachment of breast cancer cells

Oncotarget
Lekhana BhandaryStuart S Martin

Abstract

The presence of circulating tumor cells (CTCs) in blood predicts poor patient outcome and CTC frequency is correlated with higher risk of metastasis. Recently discovered, novel microtubule-based structures, microtentacles, can enhance reattachment of CTCs to the vasculature. Microtentacles are highly dynamic membrane protrusions formed in detached cells and occur when physical forces generated by the outwardly expanding microtubules overcome the contractile force of the actin cortex. Rho-associated kinase (ROCK) is a major regulator of actomyosin contractility and Rho/ROCK over-activation is implicated in tumor metastasis. ROCK inhibitors are gaining popularity as potential cancer therapeutics based on their success in reducing adherent tumor cell migration and invasion. However, the effect of ROCK inhibition on detached cells in circulation is largely unknown. In this study, we use breast tumor cells in suspension to mimic detached CTCs and show that destabilizing the actin cortex through ROCK inhibition in suspended cells promotes the formation of microtentacles and enhances reattachment of cells from suspension. Conversely, increasing actomyosin contraction by Rho over-activation reduces microtentacle frequency and reattachm...Continue Reading

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Citations

Jun 9, 2016·Endocrine-related Cancer·Ahmad M AlamriPriscilla A Furth
Oct 1, 2015·Pharmacological Reviews·Gervaise Loirand
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Nov 20, 2020·Scientific Reports·Julia Tarnoki-ZachAndras Czirok
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Dec 7, 2020·Translational Research : the Journal of Laboratory and Clinical Medicine·Uttara SaranChendil Damodaran

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