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Overexpression of RHO Inhibitor and PAK as Possible Treatments For Restoring Sharp Features in Cancer Cells

Published online by Cambridge University Press:  02 July 2020

Heckman C. A.
Affiliation:
Center for Microscopy & Microanalysis
Urban J. M.
Affiliation:
Center for Microscopy & Microanalysis
Wales T. S.
Affiliation:
Center for Microscopy & Microanalysis
Cayer M. L.
Affiliation:
Center for Microscopy & Microanalysis
Barnes J. A.
Affiliation:
Computer Science Department, Bowling Green State University, Bowling Green, OH, 43403, USA
Sverdlov V.
Affiliation:
Computer Science Department, Bowling Green State University, Bowling Green, OH, 43403, USA
Hall C.
Affiliation:
Institute of Neurology, University College London, 1 Wakefield Street, London, WC1N 1PJ, UK
Kozma R.
Affiliation:
Institute of Neurology, University College London, 1 Wakefield Street, London, WC1N 1PJ, UK
Lim L.
Affiliation:
Institute of Neurology, University College London, 1 Wakefield Street, London, WC1N 1PJ, UK
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Abstract

The mechanism of action of the tumor promoter, phorbol 12-myristate 13-acetate (PMA), depends on its ability to substitute for an endogenous second messenger, diacylglycerol, and thereby activate certain members of an enzyme family known as protein kinase C. Previous work from this laboratory showed that the quantitative shape phenotype of cells treated with PMA resembled the phenotype of bona fidecancer cells. The effect of PMA on this phenotype was transient, and was restricted to a period of two- to five-hours after exposure to PMA. When the shape phenotype was dissected into components by relating different variable's values to shape features, several of the altered values appeared to rely upon a declining number of sharp features, such as filopodia and microspikes, at the cell edge.

Filopodia and microspikes are in turn regulated by a GTPase of the Rho family, Cdc42, which modulates actin architecture.

Type
The Cell Biology of Cancer (Organized by J. Jerome and B. Gunning)
Copyright
Copyright © Microscopy Society of America 2001

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