Aquaporin 3 promotes the stem-like properties of gastric cancer cells via Wnt/GSK-3β/β-catenin pathway

Zhou, Yangchun; Wang, Yao; Wen, Jianxun; Zhao, Haijian; Dong, Xuqiang; Wang, Shoulin; Shen, Lizong

doi:10.18632/oncotarget.7664

Cited by 42 publications

(45 citation statements)

References 33 publications

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“…Recently, it has been shown that AQP3 expression might be related to development of several carcinomas including gastric carcinoma [26,27], oesophageal and oral squamous cell carcinoma [28], cervical carcinoma [29] and cancers of the thyroid [30], pancreas [31], prostate [32,33], ovary [34] and skin [35,36]. In our study, AQP3 expression was observed in all tissue samples examined in LMS group except in one case.…”

Section: Resultssupporting

confidence: 62%

Can aquaporins be used as diagnostic and prognostic markers for uterine smooth muscle tumours?

Alabalık

Türkçü

Keleş

et al. 2016

Biotechnology & Biotechnological Equipment

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Generally, uterine leiomyosarcoma is easily diagnosed. However, uterine smooth muscle tumours which show atypical histological features and unusual growth patterns may mimic malignancy and may not be easily diagnosed. In this study, our aim is to show the expressions of Aquaporin3, Aquaporin7 and Aquaporin9 in uterine smooth muscle tumours, and to investigate if aquaglyceroporins can be used as diagnostic and prognostic markers to start rapidly an appropriate treatment for patients with these tumours in order to extend the survival time. We determined that there had been 74 patients diagnosed with uterine smooth muscle tumours. We divided patients into four groups based on the diagnosis: bizarre leiomyoma, smooth muscle tumour of uncertain malignant potential, leiomyosarcoma and leiomyoma. Aquaporin3, Aquaporin7 and Aquaporin9 were detected by using monoclonal anti-Aquaporin3, antiAquaporin7 and anti-Aquaporin9 antibodies, respectively. In leiomyosarcoma group, we observed a statistically significant relation of Aquaporin3 expression with survival time, grade, stage, mitotic index and Ki-67 score. A significant relation of both Aquaporin7 and Aquaporin9 expressions with survival time, grade, stage was not statistically detected in leiomyosarcoma group. The decrease of Aquaporin3 expression can be used as important diagnostic and prognostic marker. Aquaporin7 and Aquaporin9 expressions cannot be used as diagnostic and prognostic markers.

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Section: Resultssupporting

confidence: 62%

Can aquaporins be used as diagnostic and prognostic markers for uterine smooth muscle tumours?

Alabalık

Türkçü

Keleş

et al. 2016

Biotechnology & Biotechnological Equipment

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“…To investigate the effects of AQP3 on chemosensitivity in GC cells, its expression was upregulated in AGS cells and downregulated in MGC803 and SGC7901 cells by lentiviral transduction, as previously reported (Figure 1b). 12,13 AQP3 overexpression induced cDDP resistance compared with control AGS cells ( P <0.05, Figure 1c), and AQP3 knockdown increased the chemosensitivity of MGC803 and SGC7901 cells ( P <0.05, Figure 1c). Furthermore, AQP3 expression in MGC803, SGC7901 and AGS cells was significantly enhanced after cDDP treatment respectively (Figure 1d).…”

Section: Resultsmentioning

confidence: 96%

“…Immunofluorescence was conducted according to the methods reported by Zhou et al 13 A primary antibody against LC3 A/B (Cell Signaling Technology, Beverly, MA, USA) was used. The secondary antibody was obtained from Beyotime (Beyotime Institute of Biotechnology, Henan, China).…”

Section: Methodsmentioning

confidence: 99%

“…10 Our previous study demonstrated that AQP3 is overexpressed in GC tissues, that its expression is associated with histological classification, lymph node metastasis and lymphovascular invasion 7,11 and that its upregulation promotes the invasion and metastasis of GC cells via promoting the epithelial–mesenchymal transition (EMT) and the stem-like properties of gastric cancer cells. 12,13 …”

Section: Introductionmentioning

confidence: 99%

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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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“…AQP3 can transport glycerol across the cytomembrane7 and is involved in the regulation of cell proliferation and migration in both normal and tumor tissues 2,10,37,38. Overexpression of AQP3 has been reported in diverse tumors, including GC,39 colorectal cancer,40 lung carcinoma41 and esophageal and oral squamous cell carcinoma 9.…”

Section: Discussionmentioning

confidence: 99%

Silencing of AQP3 induces apoptosis of gastric cancer cells via downregulation of glycerol intake and downstream inhibition of lipogenesis and autophagy

Liang

Zhang

et al. 2017

OTT

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Gastric cancer (GC) has a poor prognosis and is a leading cause of cancer-related death. Optimal therapeutic targets have not been identified. AQP3 is capable of transporting glycerol across the cytomembrane. Previous studies have shown that AQP3 is involved in proliferation, invasion and migration by regulating glycerol and lipid metabolism in diverse cancer cell types. However, the potential roles of glycerol and lipid metabolism in AQP3-related cell apoptosis in GC remain unclear. In this study, we observed that AQP3 expression was upregulated in tumor tissues, and positively correlated with tumor size, lymph node metastasis and glycerol concentration in human GC samples. Silencing of AQP3 resulted in decreased glycerol intake and impaired lipid synthesis, which contributed to increased cell apoptosis. Furthermore, inhibition of autophagy induced by AQP3 knockdown promoted cell apoptosis. Administration of either glycerol or rapamycin restored cell viability, and overexpression of AQP3 increased cell viability by upregulating cellular glycerol metabolism and autophagy. Our study demonstrates that the increase in cell apoptosis of AQP3-deficient GC cells is a consequence of reduced glycerol uptake and lipogenesis and is associated with autophagy inhibition induced by AQP3 deficiency.

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Aquaporin 3 promotes the stem-like properties of gastric cancer cells via Wnt/GSK-3β/β-catenin pathway

Cited by 42 publications

References 33 publications

Can aquaporins be used as diagnostic and prognostic markers for uterine smooth muscle tumours?

Can aquaporins be used as diagnostic and prognostic markers for uterine smooth muscle tumours?

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

Silencing of AQP3 induces apoptosis of gastric cancer cells via downregulation of glycerol intake and downstream inhibition of lipogenesis and autophagy

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