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[Cancer Research 61, 5688-5691, August 1, 2001]
© 2001 American Association for Cancer Research

Advances in Brief

PTEN-independent Induction of Caspase-mediated Cell Death and Reduced Invasion by the Focal Adhesion Targeting Domain (FAT) in Human Astrocytic Brain Tumors Which Highly Express Focal Adhesion Kinase (FAK)1

Graham Jones, Joel Machado, Jr., Markus Tolnay and Adrian Merlo2

Laboratory of Molecular Neuro-Oncology, Department of Clinical and Biological Sciences [G. J., J. M., A. M.], Department of Surgery [A. M.], and the Institute for Pathology [M. T.], University of Basel, 4031 Basel, Switzerland

Increased expression of focal adhesion kinase (FAK) was consistently observed in low- and high-grade astrocytomas and during glioblastoma progression after radiotherapy, but not in the more benign oligodendroglioma. In glioblastoma cell lines deficient for p53, p16INK4A, and p14ARF, FAK was inhibited in a dominant-negative manner by the focal adhesion targeting (FAT) domain, reducing invasion. In addition, caspase-3 activity was increased after serum withdrawal, or by cisplatin in the presence of serum, or upon loss of substrate attachment, and was in each case independent of PTEN status. Our results identify FAK as a potential target for anti-invasive strategies against infiltrating glioma cells.




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Copyright © 2001 by the American Association for Cancer Research.