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Aquaporin-5: from structure to function and dysfunction in cancer

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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.

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Abbreviations

AQP:

Aquaporin

cAMP:

Cyclic adenosine monophosphate

CDK:

Cyclin-dependent kinases

CHIP28:

Channel-like integral protein of 28 kDa

CML:

Chronic myelogenous leukemia

CRC:

Colorectal cancer

EGCG:

Epigallocatechin gallate

EGFR:

Epidermal growth factor receptor

EMT:

Epithelial mesenchymal transition

ERK1/2:

Extracellular signal-regulated kinases 1 and 2

FAK:

Focal adhesion kinase

HCC:

Hepatocellular carcinoma

HIF-1α:

Hypoxia inducible factor

HER2:

Epidermal growth factor receptor 2

IκBα:

Nuclear factor-κB inhibitor alpha

MAPK:

Mitogen-activated protein kinases

MIP:

Major intrinsic protein

MDR:

Multidrug resistance

NAFTA5:

Nuclear factor of activated T-cells 5

NF-κB:

Nuclear factor-κB

NPA:

Asparagine–proline–alanine

NSCLC:

Non-small cell lung cancer

PI3K:

Phosphatidylinositol-3-kinase

PKA:

Protein kinase A

SCC:

Squamous cell carcinoma

Sp1:

Specificity protein 1

TNM:

Tumor-nodes-metastasis

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Acknowledgments

This work was supported by Fundação para a Ciência e a Tecnologia (PEst-OE/SAU/UI4013/2011–2014 to iMed.ULisboa).

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  1. Research Institute for Medicines (iMed.ULisboa), Faculty of Pharmacy, Universidade de Lisboa, 1649-003, Lisbon, Portugal

    Inês Direito, Ana Madeira, Maria Alexandra Brito & Graça Soveral

  2. Department of Biochemistry and Human Biology, Faculty of Pharmacy, Universidade de Lisboa, Lisbon, Portugal

    Inês Direito, Ana Madeira, Maria Alexandra Brito & Graça Soveral

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  1. Inês Direito
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Correspondence to Graça Soveral.

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Direito, I., Madeira, A., Brito, M.A. et al. Aquaporin-5: from structure to function and dysfunction in cancer. Cell. Mol. Life Sci. 73, 1623–1640 (2016). https://doi.org/10.1007/s00018-016-2142-0

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