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Aquaporins—new players in cancer biology

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Abstract

The aquaporins (AQPs) are small, integral-membrane proteins that selectively transport water across cell plasma membranes. A subset of AQPs, the aquaglyceroporins, also transport glycerol. AQPs are strongly expressed in tumor cells of different origins, particularly aggressive tumors. Recent discoveries of AQP involvement in cell migration and proliferation suggest that AQPs play key roles in tumor biology. AQP1 is ubiquitously expressed in tumor vascular endothelium, and AQP1-null mice show defective tumor angiogenesis resulting from impaired endothelial cell migration. AQP-expressing cancer cells show enhanced migration in vitro and greater local tumor invasion, tumor cell extravasation, and metastases in vivo. AQP-dependent cell migration may involve AQP-facilitated water influx into lamellipodia at the front edge of migrating cells. The aquaglyceroporin AQP3, which is found in normal epidermis and becomes upregulated in basal cell carcinoma, facilitates cell proliferation in different cell types. Remarkably, AQP3-null mice are resistant to skin tumorigenesis by a mechanism that may involve reduced tumor cell glycerol metabolism and ATP generation. Together, the data suggest that AQP expression in tumor cells and tumor vessels facilitates tumor growth and spread, suggesting AQP inhibition as a novel antitumor therapy.

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Acknowledgements

Supported by grants EB00415, DK35124, EY13574, HL59198, DK72517, and HL73856 from the National Institutes of Health, and Research Development Program and Drug Discovery grants from the Cystic Fibrosis Foundation (to ASV) and by a Wellcome Trust Clinician–Scientist Fellowship and grants from the Neurosciences Research Foundation (to MCP).

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Authors and Affiliations

  1. Departments of Medicine and Physiology, University of California, 1246 Health Sciences East Tower, San Francisco, CA, 94143-0521, USA

    A. S. Verkman, Mariko Hara-Chikuma & Marios C. Papadopoulos

  2. Department of Dermatology, Graduate School of Medicine, Kyoto University, Kyoto, Japan

    Mariko Hara-Chikuma

  3. Academic Neurosurgery Unit, St. George’s, University of London, London, UK

    Marios C. Papadopoulos

Authors
  1. A. S. Verkman
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  2. Mariko Hara-Chikuma
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  3. Marios C. Papadopoulos
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Correspondence to A. S. Verkman.

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Verkman, A.S., Hara-Chikuma, M. & Papadopoulos, M.C. Aquaporins—new players in cancer biology. J Mol Med 86, 523–529 (2008). https://doi.org/10.1007/s00109-008-0303-9

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  • DOI: https://doi.org/10.1007/s00109-008-0303-9

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