Aquaporins as diagnostic and therapeutic targets in cancer: How far we are?

Wang, Jian; Li, Feng; Zhu, Zhou; Zheng, Minghuan; Wang, Diane; Chen, Zhihong; Sun, Hongzhi

doi:10.1186/s12967-015-0439-7

Cited by 110 publications

(114 citation statements)

References 108 publications

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“…Increased transcript levels of HsAQP1 , also sometimes accompanied by other aquaporins, have been commonly reported for cancerous cells1920, with the level of HsAQP1 expression often correlated with cell growth, grade of tumor2021, and metastasis2223. It has been also reported that the deletion of HsAQP1 was effective in reducing breast tumor size and lung metastasis23 and HsAQP1 silencing inhibited the proliferation and invasiveness of osteosarcoma cells24.…”

Section: Discussionmentioning

confidence: 94%

Significance of oxygen transport through aquaporins

Zwiazek

Tan

et al. 2017

Sci Rep

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Aquaporins are membrane integral proteins responsible for the transmembrane transport of water and other small neutral molecules. Despite their well-acknowledged importance in water transport, their significance in gas transport processes remains unclear. Growing evidence points to the involvement of plant aquaporins in CO2 delivery for photosynthesis. The role of these channel proteins in the transport of O2 and other gases may also be more important than previously envisioned. In this study, we examined O2 permeability of various human, plant, and fungal aquaporins by co-expressing heterologous aquaporin and myoglobin in yeast. Two of the most promising O2-transporters (Homo sapiens AQP1 and Nicotiana tabacum PIP1;3) were confirmed to facilitate O2 transport in the spectrophotometric assay using yeast protoplasts. The over-expression of NtPIP1;3 in yeasts significantly increased their O2 uptake rates in suspension culture. In N. tabacum roots subjected to hypoxic hydroponic conditions, the transcript levels of the O2-transporting aquaporin NtPIP1;3 significantly increased after the seven-day hypoxia treatment, which was accompanied by the increase of ATP levels in the apical root segments. Our results suggest that the functional significance of aquaporin-mediated O2 transport and the possibility of controlling the rate of transmembrane O2 transport should be further explored.

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Section: Discussionmentioning

confidence: 94%

Significance of oxygen transport through aquaporins

Zwiazek

Tan

et al. 2017

Sci Rep

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“…10,17 Apart from its expected physiological functions, including urine concentration and exocrine gland secretion, as well as several unanticipated functions, including brain swelling, neural signal transduction, skin moisturization and fat metabolism, it has been implicated in tumorigenesis and tumor progression. 10,18 AQP3 has been found to be overexpressed in a wide variety of cancer types, and its overexpression has been demonstrated to be associated with tumor invasion, metastasis and poor survival.…”

Section: Discussionmentioning

confidence: 99%

Aquaporin 3 facilitates chemoresistance in gastric cancer cells to cisplatin via autophagy

Dong

Wang

Zhou

et al. 2016

Cell Death Discovery

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Cisplatin (cDDP) remains one of the first-line chemotherapeutic agents for gastric cancer (GC) treatment, and resistance to cDDP is the major limitation in its clinical application. Mechanisms of cDDP resistance have been shown to be varied and complicated. Aquaporin 3 (AQP3) has been demonstrated to be overexpressed in GC tissues and is thought to be involved in GC carcinogenesis and progression. However, the role of AQP3 in chemosensitivity of GC to cytotoxic agents remains unknown. In this study, we show that AQP3 overexpression induced resistance to cDDP in AGS cells (P<0.05), and AQP3 knockdown increased the chemosensitivity in MGC803 and SGC7901 cells (P<0.05). Moreover, cDDP treatment enhanced AQP3 expression in MGC803, SGC7901 and AGS cells. AQP3 overexpression promoted the conversion of LC3-I to LC3-II in AGS cells, whereas AQP3 knockdown inhibited this conversion in MGC803 and SGC7901 cells. AQP3 upregulation increased Atg5 and Beclin-1 expression, and inhibited P62 expression in AGS cells, whereas AQP3 knockdown showed the opposite results in MGC803 and SGC7901 cells. Chloroquine (CQ), an autophagy inhibitor, enhanced the cytotoxicity of cDDP in GC cells, and CQ reversed the chemoresistance to cDDP caused by AQP3 overexpression in GC cells. Together, our data demonstrate that AQP3 facilitates cisplatin resistance in gastric cancer cells via autophagy, and suggest that the development of AQP3-based tumor therapeutics could play a key role in future GC treatment strategies.

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“…A number of studies have demonstrated that AQP5 promoted the proliferation and metastasis of CRC . Moreover, considerable clinical data suggest that high expression of AQP5 predicted tumor metastasis and poor prognosis of CRC . Nonetheless, the molecular mechanisms of AQP5 involved in CRC metastasis remain elusive.…”

Section: Introductionmentioning

confidence: 99%

Down‐regulation of aquaporin 5‐mediated epithelial‐mesenchymal transition and anti‐metastatic effect by natural product Cairicoside E in colorectal cancer

Chen

Zhang

et al. 2017

Molecular Carcinogenesis

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Epithelial-mesenchymal transition (EMT) has emerged as an important determinant role in colorectal cancer (CRC) metastasis. It has been reported that aquaporin 5 (AQP5) is closely linked to CRC metastasis. However, the effect of AQP5 on the EMT process of CRC remains unknown. The current study showed that overexpression of AQP5 activated EMT in CRC cells. Cairicoside E (CE), a natural resin glycoside compound isolated from Ipomoea cairica, showed promising cytotoxic activity in our previous report. Further investigation found that CE inhibited the expression of AQP5 and the EMT process. Moreover, the inhibitory effect of CE on EMT was reversed by overexpression of AQP5. Importantly, CE also suppressed the EMT and p-Smad2/3 induced by TGF-β1. On the other hand, overexpression of AQP5 up-regulated the p-Smad2/3, which resulted in the activation of EMT. After silencing of AQP5, CE had no significant effect on EMT markers and p-Smad2/3 induced by TGF-β1, indicating that CE inhibited the EMT through down-regulation of AQP5 and suppression of p-Smad2/3. CE also inhibited the AQP5 expression in the lung metastatic nodules of HCT-116 cells in vivo. Our findings suggested that CE may serve as a promising drug for the treatment of CRC metastasis.

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Aquaporins as diagnostic and therapeutic targets in cancer: How far we are?

Cited by 110 publications

References 108 publications

Significance of oxygen transport through aquaporins

Significance of oxygen transport through aquaporins

Aquaporin 3 facilitates chemoresistance in gastric cancer cells to cisplatin via autophagy

Down‐regulation of aquaporin 5‐mediated epithelial‐mesenchymal transition and anti‐metastatic effect by natural product Cairicoside E in colorectal cancer

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