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Jessica D Arden, Kari I Lavik, Kaitlin A Rubinic, Nicolas Chiaia, Sadik A Khuder, Marthe J Howard, Andrea L Nestor-Kalinoski, Arthur S Alberts, Kathryn M Eisenmann
The extensive invasive capacity of glioblastoma (GBM) makes it resistant to surgery, radiotherapy, and chemotherapy and thus makes it lethal. In vivo, GBM invasion is mediated by Rho GTPases through unidentified downstream effectors. Mammalian Diaphanous (mDia) family formins are Rho-directed effectors that regulate the F-actin cytoskeleton to support tumor cell motility. Historically, anti-invasion strategies focused upon mDia inhibition, whereas activation remained unexplored. The recent development of small molecules directly inhibiting or activating mDia-driven F-actin assembly that supports motility allows for exploration of their role in GBM...
November 1, 2015: Molecular Biology of the Cell
L Leanne Lash, Bradley J Wallar, Julie D Turner, Steven M Vroegop, Robert E Kilkuskie, Susan M Kitchen-Goosen, H Eric Xu, Arthur S Alberts
Although the cancer cell cytoskeleton is a clinically validated target, few new strategies have emerged for selectively targeting cell division by modulating the cytoskeletal structure, particularly ways that could avoid the cardiotoxic and neurotoxic effects of current agents such as taxanes. We address this gap by describing a novel class of small-molecule agonists of the mammalian Diaphanous (mDia)-related formins, which act downstream of Rho GTPases to assemble actin filaments, and their organization with microfilaments to establish and maintain cell polarity during migration and asymmetric division...
November 15, 2013: Cancer Research
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