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Signalling via integrins: Implications for cell survival and anticancer strategies
Author(s): Hehlgans S (Hehlgans, Stephanie), Haase M (Haase, Michael), Cordes N (Cordes, Nils)
Source: BIOCHIMICA ET BIOPHYSICA ACTA-REVIEWS ON CANCER    Volume: 1775    Issue: 1    Pages: 163-180    Published: JAN 2007  
Times Cited: 79     References: 232     
Abstract: Integrin-associated signalling renders cells more resistant to genotoxic anti-cancer agents like ionizing radiation and chemotherapeutic substances, a phenomenon termed cell adhesion-mediated radioresistance/drug resistance (CAM-RR, CAM-DR). Integrins are heterodimeric cell-surface molecules that on one side link the actin cytoskeleton to the cell membrane and on the other side mediate cell-matrix interactions. In addition to their structural functions, integrins mediate signalling from the extracellular space into the cell through integrin-associated signalling and adaptor molecules such as FAK (focal adhesion kinase), ILK (integrin-linked kinase), PINCH (particularly interesting new cysteine-histidine rich protein) and Nck2 (non-catalytic (region of) tyrosine kinase adaptor protein 2). Via these molecules, integrin signalling tightly and cooperatively interacts with receptor tyrosine kinase signalling to regulate survival, proliferation and cell shape as well as polarity, adhesion, migration and differentiation. In tumour cells of diverse origin like breast, colon or skin, the function and regulation of these molecules is partly disturbed and thus might contribute to the malignant phenotype and pre-existent and acquired multidrug resistance. These issues as well as a variety of therapeutic options envisioned to influence tumour cell growth, metastasis and resistance, including kinase inhibitors, anti-integrin antibodies or RNA interference, will be summarized and discussed in this review. (c) 2006 Elsevier B.V. All rights reserved.
Document Type: Review
Language: English
Reprint Address: Cordes, N (reprint author), Tech Univ Dresden, OncoRay Ctr Radiat Res Oncol, Med Fac Carl Gustav Carus, Fetscherstasse 74,PF 86, D-01307 Dresden, Germany
Addresses:
1. Tech Univ Dresden, OncoRay Ctr Radiat Res Oncol, Med Fac Carl Gustav Carus, D-01307 Dresden, Germany
Publisher: ELSEVIER SCIENCE BV, PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS
Subject Category: Biochemistry & Molecular Biology; Biophysics; Oncology
IDS Number: 123TD
ISSN: 0304-419X
DOI: 10.1016/j.bbcan.2006.09.001
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