title: Aquaporin-5: from structure to function and dysfunction in cancer.
abstract: Aquaporins, a highly conserved group of membrane proteins, are involved in the bidirectional transfer of water and small solutes across cell membranes taking part in many biological functions all over the human body. In view of the wide range of cancer malignancies in which aquaporin-5 (AQP5) has been detected, an increasing interest in its implication in carcinogenesis has emerged. Recent publications suggest that this isoform may enhance cancer cell proliferation, migration and survival in a variety of malignancies, with strong evidences pointing to AQP5 as a promising drug target and as a novel biomarker for cancer aggressiveness with high translational potential for therapeutics and diagnostics. This review addresses the structural and functional features of AQP5, detailing its tissue distribution and functions in human body, its expression pattern in a variety of tumors, and highlighting the underlying mechanisms involved in carcinogenesis. Finally, the actual progress of AQP5 research, implications in cancer biology and potential for cancer detection and prognosis are discussed.
authors.affiliation: Research Institute for Medicines (iMed.ULisboa), Faculty of Pharmacy, Universidade de Lisboa, 1649-003, Lisbon, Portugal.|Department of Biochemistry and Human Biology, Faculty of Pharmacy, Universidade de Lisboa, Lisbon, Portugal.
authors.forename: Inês
authors.initials: I
authors.lastname: Direito
authors.affiliation: Research Institute for Medicines (iMed.ULisboa), Faculty of Pharmacy, Universidade de Lisboa, 1649-003, Lisbon, Portugal.|Department of Biochemistry and Human Biology, Faculty of Pharmacy, Universidade de Lisboa, Lisbon, Portugal.
authors.forename: Ana
authors.initials: A
authors.lastname: Madeira
authors.affiliation: Research Institute for Medicines (iMed.ULisboa), Faculty of Pharmacy, Universidade de Lisboa, 1649-003, Lisbon, Portugal.|Department of Biochemistry and Human Biology, Faculty of Pharmacy, Universidade de Lisboa, Lisbon, Portugal.
authors.forename: Maria Alexandra
authors.initials: MA
authors.lastname: Brito
authors.affiliation: Research Institute for Medicines (iMed.ULisboa), Faculty of Pharmacy, Universidade de Lisboa, 1649-003, Lisbon, Portugal. gsoveral@ff.ul.pt.|Department of Biochemistry and Human Biology, Faculty of Pharmacy, Universidade de Lisboa, Lisbon, Portugal. gsoveral@ff.ul.pt.
authors.forename: Graça
authors.identifier: http://orcid.org/0000-0001-8487-110X
authors.initials: G
authors.lastname: Soveral
mesh_terms: D051402:Aquaporin 5 / Q000378:metabolism*; D001692:Biological Transport / Q000502:physiology; D002462:Cell Membrane / Q000378:metabolism*; D002465:Cell Movement / Q000502:physiology; D049109:Cell Proliferation / Q000502:physiology; D002470:Cell Survival / Q000502:physiology; D006801:Humans; D008565:Membrane Proteins / Q000378:metabolism; D009369:Neoplasms / Q000473:pathology*; D020033:Protein Isoforms / Q000378:metabolism*; D014867:Water / Q000378:metabolism
chemical_list: D051402:Aquaporin 5; D008565:Membrane Proteins; D020033:Protein Isoforms; D014867:Water
keywords: Aquaporin; Biomarker; Permeability; Signaling pathways; Tumor; Water channel
references.citation: Science. 2001 Dec 14;294(5550):2353-7
references.pmid: 11743202
references.citation: Cell Physiol Biochem. 2010;26(3):375-82
references.pmid: 20798522
references.citation: Acta Pharmacol Sin. 2007 Aug;28(8):1166-74
references.pmid: 17640479
references.citation: Science. 1992 Apr 17;256(5055):385-7
references.pmid: 1373524
references.citation: PLoS One. 2013;8(3):e57541
references.pmid: 23469202
references.citation: IUBMB Life. 2015 Jan;67(1):54-60
references.pmid: 25631586
references.citation: J Biol Chem. 2005 Feb 4;280(5):3590-6
references.pmid: 15536076
references.citation: Am J Physiol. 1998 Feb;274(2):C543-8
references.pmid: 9486145
references.citation: Biochim Biophys Acta. 2015 Oct;1848(10 Pt B):2576-83
references.pmid: 25204262
references.citation: World J Surg Oncol. 2014 Sep 13;12:284
references.pmid: 25217331
references.citation: J Bacteriol. 1997 May;179(10):3365-7
references.pmid: 9150238
references.citation: Biochim Biophys Acta. 2014 May;1840(5):1507-12
references.pmid: 24189537
references.citation: Proc Natl Acad Sci U S A. 2010 Sep 7;107(36):15681-6
references.pmid: 20724658
references.citation: J Invest Dermatol. 2014 Jan;134(1):284-287
references.pmid: 23867895
references.citation: J Biol Chem. 1987 Dec 25;262(36):17497-503
references.pmid: 3121599
references.citation: Biochim Biophys Acta. 2014 May;1840(5):1605-13
references.pmid: 24120524
references.citation: Biochemistry. 1992 Aug 25;31(33):7436-40
references.pmid: 1510932
references.citation: J Cell Physiol. 2014 Nov;229(11):1787-801
references.pmid: 24676973
references.citation: Biochem Biophys Res Commun. 2008 Feb 8;366(2):321-7
references.pmid: 18042467
references.citation: J Biol Chem. 1994 Jan 21;269(3):1668-73
references.pmid: 7507481
references.citation: J Mammary Gland Biol Neoplasia. 2006 Oct;11(3-4):249-68
references.pmid: 17136613
references.citation: Biophys Chem. 2013 Jan;171:24-30
references.pmid: 23176748
references.citation: J Biol Chem. 2003 Aug 22;278(34):32173-80
references.pmid: 12783871
references.citation: Int J Oncol. 2012 Jul;41(1):67-75
references.pmid: 22576684
references.citation: Am J Rhinol Allergy. 2012 May-Jun;26(3):167-71
references.pmid: 22643939
references.citation: Med Oncol. 2012 Mar;29(1):205-11
references.pmid: 21193966
references.citation: Oncol Rep. 2011 Jun;25(6):1645-50
references.pmid: 21455588
references.citation: Glia. 2007 Aug 1;55(10):1034-43
references.pmid: 17549682
references.citation: Hum Pathol. 2016 Feb;48:102-10
references.pmid: 26614400
references.citation: Nature. 2005 Apr 7;434(7034):786-92
references.pmid: 15815633
references.citation: Gut. 2003 Jul;52(7):1008-16
references.pmid: 12801959
references.citation: Biol Cell. 2010 Jan;103(1):35-54
references.pmid: 21143194
references.citation: Med Oncol. 2012 Sep;29(3):1998-2004
references.pmid: 22048942
references.citation: Annu Rev Physiol. 2008;70:301-27
references.pmid: 17961083
references.citation: Cancer Res. 2006 Jun 15;66(12):6175-82
references.pmid: 16778191
references.citation: J Clin Endocrinol Metab. 2011 Sep;96(9):E1399-408
references.pmid: 21715543
references.citation: Oncol Lett. 2012 Aug;4(2):257-261
references.pmid: 22844365
references.citation: Am J Hum Genet. 2013 Aug 8;93(2):330-5
references.pmid: 23830519
references.citation: Proc Natl Acad Sci U S A. 2008 Sep 9;105(36):13327-32
references.pmid: 18768791
references.citation: Tumour Biol. 2013 Jun;34(3):1743-51
references.pmid: 23436048
references.citation: Biochim Biophys Acta. 2014 May;1840(5):1524-32
references.pmid: 23954206
references.citation: Nature. 2000 Oct 5;407(6804):599-605
references.pmid: 11034202
references.citation: Biochem Biophys Res Commun. 2015 Sep 25;465(3):644-9
references.pmid: 26299924
references.citation: Nature. 1999 Nov 11;402(6758):184-7
references.pmid: 10647010
references.citation: J Biol Chem. 2007 Jan 12;282(2):1183-92
references.pmid: 17105724
references.citation: Proteins. 2010 Feb 15;78(3):661-70
references.pmid: 19842162
references.citation: PLoS One. 2013;8(4):e59897
references.pmid: 23565173
references.citation: Fertil Steril. 2010 Sep;94(4):1229-34
references.pmid: 19931078
references.citation: FEBS Lett. 2010 Jun 18;584(12):2580-8
references.pmid: 20416297
references.citation: Mol Aspects Med. 2012 Oct-Dec;33(5-6):514-7
references.pmid: 22542572
references.citation: Biochem Biophys Res Commun. 2008 Mar 7;367(2):291-8
references.pmid: 18155156
references.citation: Gynecol Oncol. 2006 Feb;100(2):294-9
references.pmid: 16242760
references.citation: Nat Rev Neurosci. 2013 Apr;14(4):265-77
references.pmid: 23481483
references.citation: Oncogene. 2003 Oct 2;22(43):6699-703
references.pmid: 14555983
references.citation: Arch Gynecol Obstet. 2012 Jan;285(1):239-45
references.pmid: 21614498
references.citation: Biochim Biophys Acta. 2006 Aug;1758(8):1053-60
references.pmid: 16712780
references.citation: J Neurooncol. 2013 Apr;112(2):297-305
references.pmid: 23392848
references.citation: J Biol Chem. 2001 Nov 2;276(44):41288-92
references.pmid: 11514581
references.citation: Cells Tissues Organs. 2005;179(1-2):73-80
references.pmid: 15942195
references.citation: World J Surg Oncol. 2012 Nov 13;10:242
references.pmid: 23148732
references.citation: Proc Natl Acad Sci U S A. 1991 Dec 15;88(24):11110-4
references.pmid: 1722319
references.citation: Nat Cell Biol. 2000 May;2(5):249-56
references.pmid: 10806474
references.citation: Biomed Pharmacother. 2010 May;64(5):313-8
references.pmid: 20106632
references.citation: Handb Exp Pharmacol. 2009;(190):185-201
references.pmid: 19096778
references.citation: Biochem Biophys Res Commun. 1997 Nov 17;240(2):324-8
references.pmid: 9388476
references.citation: PLoS One. 2008 Jul 09;3(7):e2594
references.pmid: 18612408
references.citation: J Clin Invest. 2000 Jan;105(1):93-100
references.pmid: 10619865
references.citation: Mol Med Rep. 2009 Jul-Aug;2(4):645-50
references.pmid: 21475880
references.citation: Genes Cells. 2006 Oct;11(10):1133-43
references.pmid: 16999734
references.citation: Am J Physiol Gastrointest Liver Physiol. 2001 Jul;281(1):G247-54
references.pmid: 11408278
references.citation: J Dermatol. 2012 Apr;39(4):344-9
references.pmid: 21950762
references.citation: Arch Gynecol Obstet. 2012 Feb;285(2):459-67
references.pmid: 21698451
references.citation: Am J Pathol. 2010 Aug;177(2):724-34
references.pmid: 20522648
references.citation: PLoS One. 2015 Nov 16;10(11):e0143027
references.pmid: 26569106
references.citation: J Gen Physiol. 1957 Nov 20;41(2):259-77
references.pmid: 13475690
references.citation: Biochim Biophys Acta. 2015 Sep;1850(9):1786-94
references.pmid: 25982446
references.citation: PLoS One. 2008 May 14;3(5):e2162
references.pmid: 18478076
references.citation: Mol Vis. 2008 Apr 25;14:756-61
references.pmid: 18449356
references.citation: Respir Physiol Neurobiol. 2011 May 31;176(3):110-7
references.pmid: 21315850
references.citation: Neurosurgery. 1999 Mar;44(3):579-87; discussion 587-8
references.pmid: 10069595
references.citation: Exp Eye Res. 2013 Mar;108:94-102
references.pmid: 23313152
references.citation: J Ovarian Res. 2014 Aug 15;7:78
references.pmid: 25298246
references.citation: Biochim Biophys Acta. 2014 May;1840(5):1468-81
references.pmid: 24355433
references.citation: Ann Surg Oncol. 2014 Feb;21(2):375-83
references.pmid: 24114055
references.citation: Med Oncol. 2013;30(3):636
references.pmid: 23797770
references.citation: Nat Rev Drug Discov. 2014 Apr;13(4):259-77
references.pmid: 24625825
references.citation: J Biol Chem. 1995 Jan 27;270(4):1908-12
references.pmid: 7530250
references.citation: Proc Natl Acad Sci U S A. 2002 Apr 30;99(9):6053-8
references.pmid: 11972053
references.citation: Ann Oncol. 2009 Dec;20(12):1913-27
references.pmid: 19901010
references.citation: Med Electron Microsc. 2004 Jun;37(2):71-80
references.pmid: 15221647
references.citation: Basic Res Cardiol. 2008 Nov;103(6):598-610
references.pmid: 18846354
references.citation: Nat Rev Mol Cell Biol. 2014 Mar;15(3):178-96
references.pmid: 24556840
references.citation: News Physiol Sci. 2002 Apr;17:68-72
references.pmid: 11909995
references.citation: Reprod Biol. 2012 Mar;12(1):81-9
references.pmid: 22472942
references.citation: J Biol Chem. 2002 May 24;277(21):19139-44
references.pmid: 11891232
references.citation: J Mol Biol. 2006 Jan 27;355(4):628-39
references.pmid: 16325200
references.citation: J Biol Chem. 2000 Aug 25;275(34):26507-14
references.pmid: 10849430
references.citation: Oncology. 2015;88(6):369-76
references.pmid: 25721378
references.citation: Free Radic Res. 2010 May;44(5):479-96
references.pmid: 20370557
references.citation: Nature. 2006 Mar 30;440(7084):688-91
references.pmid: 16572174
references.citation: J Mol Med (Berl). 2008 May;86(5):523-9
references.pmid: 18311471
references.citation: J Gen Physiol. 1960 May;43:43-56
references.pmid: 13844488
references.citation: Science. 2013 Jun 14;340(6138):1346-1349
references.pmid: 23766328
references.citation: Oncol Lett. 2015 Jun;9(6):2799-2804
references.pmid: 26137150
references.citation: Mol Biol Evol. 2013 Dec;30(12):2725-9
references.pmid: 24132122
references.citation: J Struct Biol. 2011 May;174(2):315-20
references.pmid: 21251984
references.citation: J Mol Med (Berl). 2008 Feb;86(2):221-31
references.pmid: 17968524
references.citation: J Histochem Cytochem. 2004 Oct;52(10):1341-50
references.pmid: 15385580
references.citation: Biomed Res Int. 2013;2013:206525
references.pmid: 24224160
references.citation: Am J Physiol Cell Physiol. 2008 Nov;295(5):C1141-50
references.pmid: 18768929
references.citation: Cell Physiol Biochem. 2011;28(4):683-92
references.pmid: 22178880
references.citation: Am J Physiol Gastrointest Liver Physiol. 2013 Aug 1;305(3):G258-75
references.pmid: 23744739
references.citation: PLoS One. 2011;6(12):e28492
references.pmid: 22145049
references.citation: Hum Pathol. 2011 May;42(5):669-78
references.pmid: 21237499
references.citation: J Cell Biol. 1998 Dec 28;143(7):1997-2008
references.pmid: 9864370
references.citation: Mol Vis. 2010 Aug 10;16:1538-48
references.pmid: 20806077
references.citation: Am J Respir Cell Mol Biol. 2001 Mar;24(3):224-34
references.pmid: 11245621
references.citation: Cancer Lett. 2008 Jun 8;264(1):54-62
references.pmid: 18423983
references.citation: Hypertension. 2006 Jul;48(1):157-64
references.pmid: 16682607
references.citation: Adv Biol Regul. 2015 Jan;57:75-101
references.pmid: 25453219
references.citation: Biochim Biophys Acta. 2014 Dec;1846(2):312-25
references.pmid: 25080053
references.citation: J Neurosci. 2006 Jul 26;26(30):7811-9
references.pmid: 16870726
references.citation: Handb Exp Pharmacol. 2009;(190):57-76
references.pmid: 19096772
references.citation: J Biol Chem. 1991 Apr 5;266(10):6407-15
references.pmid: 2007592
references.citation: Am J Pathol. 2008 Aug;173(2):518-25
references.pmid: 18583321
references.citation: J Clin Invest. 2002 Jun;109(11):1395-9
references.pmid: 12045251
references.citation: J Biol Chem. 2002 Oct 18;277(42):39873-9
references.pmid: 12177001
references.citation: Tumour Biol. 2014 Jul;35(7):7035-45
references.pmid: 24752576
references.citation: J Pathol. 2010 Jun;221(2):210-20
references.pmid: 20455256
references.citation: J Biol Chem. 1999 Jul 16;274(29):20071-4
references.pmid: 10400615
references.citation: Histol Histopathol. 2011 Sep;26(9):1197-205
references.pmid: 21751151
references.citation: J Sex Med. 2011 Jul;8(7):1925-30
references.pmid: 21492408
references.citation: J Gastroenterol. 2014 Apr;49(4):655-66
references.pmid: 23657608
references.citation: Mol Vis. 2015 Apr 09;21:360-77
references.pmid: 25878490
references.citation: Pflugers Arch. 2005 Sep;450(6):415-28
references.pmid: 15988592
references.citation: J Dermatol Sci. 2013 Apr;70(1):26-33
references.pmid: 23473857
references.citation: Neuroscience. 2010 Jul 28;168(4):957-70
references.pmid: 19747527
references.citation: Lancet. 2001 Mar 3;357(9257):688-9
references.pmid: 11247557
references.citation: Oncol Rep. 2014 Oct;32(4):1564-70
references.pmid: 25109507
references.citation: Nat Rev Nephrol. 2010 Mar;6(3):168-78
references.pmid: 20101255
references.citation: Oncol Rep. 2012 Jun;27(6):1741-7
references.pmid: 22470085
references.citation: J Physiol Sci. 2009 Mar;59(2):113-22
references.pmid: 19340551
references.citation: J Biol Chem. 1997 May 16;272(20):13189-95
references.pmid: 9148935
references.citation: J Surg Oncol. 2012 Sep 1;106(3):267-72
references.pmid: 22105864
references.citation: Obesity (Silver Spring). 2014 Sep;22(9):2010-7
references.pmid: 24845055