Aquaporins - New players in cancer biology

A. S. Verkman, Mariko Chikuma, Marios C. Papadopoulos

Research output: Contribution to journalReview article

215 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)523-529
Number of pages7
JournalJournal of Molecular Medicine
Volume86
Issue number5
DOIs
Publication statusPublished - 2008 May
Externally publishedYes

Fingerprint

Aquaporins
Neoplasms
Aquaglyceroporins
Cell Movement
Glycerol
Cell Proliferation
Cell Membrane
Pseudopodia
Water
Basal Cell Carcinoma
Vascular Endothelium
Protein Transport
Epidermis
Membrane Proteins
Carcinogenesis
Endothelial Cells
Adenosine Triphosphate

Keywords

  • Angiogenesis
  • Aquaglyceroporin
  • Cell migration
  • Cell motility
  • Cell proliferation
  • Water channel

ASJC Scopus subject areas

  • Medicine(all)

Cite this

Aquaporins - New players in cancer biology. / Verkman, A. S.; Chikuma, Mariko; Papadopoulos, Marios C.

In: Journal of Molecular Medicine, Vol. 86, No. 5, 05.2008, p. 523-529.

Research output: Contribution to journalReview article

Verkman, A. S. ; Chikuma, Mariko ; Papadopoulos, Marios C. / Aquaporins - New players in cancer biology. In: Journal of Molecular Medicine. 2008 ; Vol. 86, No. 5. pp. 523-529.
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