Critical role of aquaporin-3 in epidermal growth factor-induced migration of colorectal carcinoma cells and its clinical significance

Li, Ang; Lu, Dongfang; Zhang, Yupeng; Li, Jia; Yu, Fang; Li, Fēi; Sun, Jiayi

doi:10.3892/or.2012.2144

Cited by 68 publications

(51 citation statements)

References 22 publications

(27 reference statements)

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“…Increasing evidence shows that a correlation exists between AQP3 expression and cancer progression and prognosis, particularly in distant or lymphatic metastasis of colorectal, esophageal, hepatocellular, and gastric malignant cancers (11)(12)(13)(14). In the current study, we showed that overexpressing AQP3 promoted the migration of breast cancer cells toward CXCL12 in association with higher intracellular H 2 O 2 levels and enhanced susceptibility to Akt activation in vitro.…”

Section: Discussionsupporting

confidence: 47%

“…AQP3 is expressed in various cancer cells derived from diverse types of cancer tissues, including breast, colon, and lung (9, 10). Recent results from clinical studies have suggested the relevance of AQP3 expression in tumor progression and the prognosis of several malignant cancers (11)(12)(13)(14). In vitro studies using cancer cell lines have implicated AQP3 expression in cancer cell proliferation and migration (15-17).…”

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confidence: 99%

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Aquaporin-3 Controls Breast Cancer Cell Migration by Regulating Hydrogen Peroxide Transport and Its Downstream Cell Signaling

Satooka

Hara‐Chikuma

2016

Molecular and Cellular Biology

108

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Most breast cancer mortality is due to clinical relapse associated with metastasis. CXCL12/CXCR4-dependent cell migration is a critical process in breast cancer progression; however, its underlying mechanism remains to be elucidated. Here, we show that the water/glycerol channel protein aquaporin-3 (AQP3) is required for CXCL12/CXCR4-dependent breast cancer cell migration through a mechanism involving its hydrogen peroxide (H 2 O 2 ) transport function. Extracellular H 2 O 2 , produced by CXCL12-activated membrane NADPH oxidase 2 (Nox2), was transported into breast cancer cells via AQP3. Transient H 2 O 2 accumulation was observed around the membrane during CXCL12-induced migration, which may be facilitated by the association of AQP3 with Nox2. Intracellular H 2 O 2 then oxidized PTEN and protein tyrosine phosphatase 1B (PTP1B) followed by activation of the Akt pathway. This contributed to directional cell migration. The expression level of AQP3 in breast cancer cells was related to their migration ability both in vitro and in vivo through CXCL12/CXCR4-or H 2 O 2 -dependent pathways. Coincidentally, spontaneous metastasis of orthotopic xenografts to the lung was reduced upon AQP3 knockdown. These findings underscore the importance of AQP3-transported H 2 O 2 in CXCL12/CXCR4-dependent signaling and migration in breast cancer cells and suggest that AQP3 has potential as a therapeutic target for breast cancer. Breast cancer mortality remains high owing to clinical relapse associated with metastases, primarily to the lungs, brain, and bones (1). Metastases are the result of several sequential processes, including cell migration and invasion (2). Organ-specific metastasis requires chemokine-dependent cancer cell migration toward destination sites (3). In particular, the CXCL12/CXCR4 axis is a key step in breast cancer cell migration toward the lungs (4, 5). The binding of CXCL12 to CXCR4 stimulates downstream G protein signaling, leading to the activation of the phosphatidylinositol 3-kinase (PI3K)/Akt or mitogen-activated protein kinase (MAPK) pathway. These effects regulate a variety of cellular functions, such as cell proliferation and migration, thereby contributing to cancer metastasis and progression (6). However, the underlying mechanism by which the pathways downstream of CXCL12/ CXCR4 result in breast cancer cell migration and metastasis remain to be fully elucidated.Aquaporin-3 (AQP3), a member of the aquaporin water channel family (AQP0 to -12), has the primary function of transporting water and glycerol (7,8). AQP3 is expressed in various cancer cells derived from diverse types of cancer tissues, including breast, colon, and lung (9, 10). Recent results from clinical studies have suggested the relevance of AQP3 expression in tumor progression and the prognosis of several malignant cancers (11)(12)(13)(14). In vitro studies using cancer cell lines have implicated AQP3 expression in cancer cell proliferation and migration (15-17). However, the mechanism by which AQP3 participates as a biological pore channe...

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Section: Discussionsupporting

confidence: 47%

mentioning

confidence: 99%

Aquaporin-3 Controls Breast Cancer Cell Migration by Regulating Hydrogen Peroxide Transport and Its Downstream Cell Signaling

Satooka

Hara‐Chikuma

2016

Molecular and Cellular Biology

108

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“…Although the expression of AQP3 was not associated with survival of colon cancer in the current study, several studies have reported on the prognostic significance of AQPs in solid tumors [12,24,25]. For example, human epidermal growth factor increased the expression of AQP3 and enhanced the migration ability of a human colorectal cancer cell line in an in vitro study.…”

Section: Discussionmentioning

confidence: 81%

“…Interestingly, Yoshida et al [11 ]reported a correlation between a low expression of aquaporin-1 (AQP1) and a better prognosis for patients with stage II and III colon cancer. A recent study has also shown that the expression of aquaporin-3 (AQP3) was associated with differentiation, lymph node metastasis, and distant metastasis of colorectal cancer [12]. Therefore, these findings suggest that AQPs may be a potential prognostic marker in patients with colon cancer and could be a novel target for anticolon cancer treatment.…”

Section: Introductionmentioning

confidence: 97%

Expression of Aquaporin-1, Aquaporin-3, and Aquaporin-5 Correlates with Nodal Metastasis in Colon Cancer

et al. 2015

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Objectives: The clinical significance of aquaporin-1 (AQP1), aquaporin-3 (AQP3), and aquaporin-5 (AQP5) expression was analyzed in a large number of patients with colon cancer. Methods: AQP1, AQP3, and AQP5 expression was investigated based on the immunohistochemistry of tissue microarray specimens from 486 colon cancer patients who underwent curative surgery. Scores were given to the staining intensity and percentage of positive cells, and the staining score was defined as the sum of these scores then used to categorize the AQP expression as negative, weakly AQP-positive, or strongly AQP-positive. Results: A total of 298 (61.3%) patients were identified as strongly AQP1-positive (staining score ≥6), while 38 (7.8%) were strongly AQP3-positive and 145 (29.8%) were strongly AQP5-positive. The overexpression of AQP1, AQP3, and AQP5 was significantly correlated with lymph node metastasis in a multivariate logistic analysis (AQP1, p = 0.026; AQP3, p = 0.023; AQP5, p = 0.003). While the multivariate survival analysis, which included age, histology, TNM stage, and CEA level showed that the expression of AQP1, AQP3, and AQP5 had no effect on the overall survival and disease-free survival. Conclusions: The current study found a significant correlation between AQP1, AQP3, and AQP5 expression and lymph node metastasis in patients with surgically resected colon cancer.

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“…Cuphen cytotoxic activity was evaluated against different mammalian cell lines, all representative of [18,47] and the MNT-1 (melanotic neuroectodermal tumor) [48], as well as a nontumorigenic human keratinocyte cell line, HaCaT [49,50]. Aiming for possible future in vivo studies, two murine cell lines were also included: B16F10 (for melanoma) [3] and C26 (for colon cancer) [51,52]. In this study, Cuphen proved to be effective by inhibiting cellular viability for all the evaluated cell lines in the range of the concentrations tested (from 0.625 to 20 μM).…”

Section: Antiproliferative Effects Of Metal Compounds In Cancer Cellsmentioning

confidence: 99%

Nanoformulations of a Potent copper-based Aquaporin Inhibitor With Cytotoxic Effect Against Cancer Cells

Nave

Castro

Rodrigues

et al. 2016

Nanomedicine (Lond.)

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Aim: Development of liposomal formulations of Cuphen, a potent copper-based aquaporin inhibitor with therapeutic potential against melanoma and colon cancer. Materials & methods: Cuphen was incorporated into liposomes using the dehydrationrehydration method. The ability of Cuphen to induce cancer cell death was evaluated by MTS and ViaCount assays. In vivo toxicity studies were performed in BALB/c mice. Results:In vitro studies illustrated the antiproliferative effects of Cuphen in different cancer cell lines, in free form or after incorporation into liposomes. In vivo studies revealed no toxic effects after parenteral administration of Cuphen liposomes. Conclusions: Cuphen liposomes are highly attractive to be further tested in murine models due to the possibility of stabilizing and specifically deliver this metallodrug to tumor sites.

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Critical role of aquaporin-3 in epidermal growth factor-induced migration of colorectal carcinoma cells and its clinical significance

Cited by 68 publications

References 22 publications

Aquaporin-3 Controls Breast Cancer Cell Migration by Regulating Hydrogen Peroxide Transport and Its Downstream Cell Signaling

Aquaporin-3 Controls Breast Cancer Cell Migration by Regulating Hydrogen Peroxide Transport and Its Downstream Cell Signaling

Expression of Aquaporin-1, Aquaporin-3, and Aquaporin-5 Correlates with Nodal Metastasis in Colon Cancer

Nanoformulations of a Potent copper-based Aquaporin Inhibitor With Cytotoxic Effect Against Cancer Cells

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