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The common fragile site FRA16D gene product WWOX: roles in tumor suppression and genomic stability

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Abstract

The fragile WWOX gene, encompassing the chromosomal fragile site FRA16D, is frequently altered in human cancers. While vulnerable to DNA damage itself, recent evidence has shown that the WWOX protein is essential for proper DNA damage response (DDR). Furthermore, the gene product, WWOX, has been associated with multiple protein networks, highlighting its critical functions in normal cell homeostasis. Targeted deletion of Wwox in murine models suggests its in vivo requirement for proper growth, metabolism, and survival. Recent molecular and biochemical analyses of WWOX functions highlighted its role in modulating aerobic glycolysis and genomic stability. Cumulatively, we propose that the gene product of FRA16D, WWOX, is a functionally essential protein that is required for cell homeostasis and that its deletion has important consequences that contribute to the neoplastic process. This review discusses the essential role of WWOX in tumor suppression and genomic stability and how its alteration contributes to cancer transformation.

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Authors and Affiliations

  1. The Lautenberg Center for Immunology and Cancer Research, IMRIC, Faculty of Medicine, Hebrew University of Jerusalem, 91220, Jerusalem, Israel

    Rami I. Aqeilan, Muhannad Abu-Remaileh & Mohammad Abu-Odeh

  2. Department of Molecular Virology, Immunology and Medical Genetics, The Ohio State University Wexner Medical Center, Columbus, OH, 43210, USA

    Rami I. Aqeilan

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  1. Rami I. Aqeilan
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  2. Muhannad Abu-Remaileh
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  3. Mohammad Abu-Odeh
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Correspondence to Rami I. Aqeilan.

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Aqeilan, R.I., Abu-Remaileh, M. & Abu-Odeh, M. The common fragile site FRA16D gene product WWOX: roles in tumor suppression and genomic stability. Cell. Mol. Life Sci. 71, 4589–4599 (2014). https://doi.org/10.1007/s00018-014-1724-y

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  • DOI: https://doi.org/10.1007/s00018-014-1724-y

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