AQP9 promotes astrocytoma cell invasion and motility via the AKT pathway

Lv, Yao; Huang, Qiang; Dai, Weimin; Jie, Yuanqing; Yu, Guofeng; Fan, Xiaofeng; Wu, An‐Bang; Qin, Miao

doi:10.3892/ol.2018.9361

Cited by 16 publications

(15 citation statements)

References 20 publications

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“…AQP4 isoforms are able to form heterotetramers, which can turn assemble into higher-order structures called orthogonal arrays of particles, indicating a link to actin cytoskeleton [ 115 ]. AQP9 is not highly expressed in normal brain; however, increased levels observed in human glioma were correlated with pathological grade [ 108 ] and are proposed to promote cell invasiveness via an AKT signaling pathway [ 110 ].…”

Section: Resultsmentioning

confidence: 99%

Combined Systematic Review and Transcriptomic Analyses of Mammalian Aquaporin Classes 1 to 10 as Biomarkers and Prognostic Indicators in Diverse Cancers

Chow

Bowen

Yool

2020

Cancers

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Aquaporin (AQP) channels enable regulated transport of water and solutes essential for fluid homeostasis, but they are gaining attention as targets for anticancer therapies. Patterns of AQP expression and survival rates for patients were evaluated by systematic review (PubMed and Embase) and transcriptomic analyses of RNAseq data (Human Protein Atlas database). Meta-analyses confirmed predominantly negative associations between AQP protein and RNA expression levels and patient survival times, most notably for AQP1 in lung, breast and prostate cancers; AQP3 in esophageal, liver and breast cancers; and AQP9 in liver cancer. Patterns of AQP expression were clustered for groups of cancers and associated with risk of death. A quantitative transcriptomic analysis of AQP1-10 in human cancer biopsies similarly showed that increased transcript levels of AQPs 1, 3, 5 and 9 were most frequently associated with poor survival. Unexpectedly, increased AQP7 and AQP8 levels were associated with better survival times in glioma, ovarian and endometrial cancers, and increased AQP11 with better survival in colorectal and breast cancers. Although molecular mechanisms of aquaporins in pathology or protection remain to be fully defined, results here support the hypothesis that overexpression of selected classes of AQPs differentially augments cancer progression. Beyond fluid homeostasis, potential roles for AQPs in cancers (suggested from an expanding appreciation of their functions in normal tissues) include cell motility, membrane process extension, transport of signaling molecules, control of proliferation and apoptosis, increased mechanical compliance, and gas exchange. AQP expression also has been linked to differences in sensitivity to chemotherapy treatments, suggesting possible roles as biomarkers for personalized treatments. Development of AQP pharmacological modulators, administered in cancer-specific combinations, might inspire new interventions for controlling malignant carcinomas.

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Section: Resultsmentioning

confidence: 99%

Combined Systematic Review and Transcriptomic Analyses of Mammalian Aquaporin Classes 1 to 10 as Biomarkers and Prognostic Indicators in Diverse Cancers

Chow

Bowen

Yool

2020

Cancers

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“…Studies have revealed that AQP9 was abundantly expressed in human glioma tissues, which is also correlated with the pathological grade of tumors [18]. AQP9 reduced the expression of E-cad and enhanced astrocytoma cell proliferation and migration through activating RAC serine/threonine protein kinase pathway [19]. Moreover, Huang et al [20].…”

Section: Discussionmentioning

confidence: 99%

Aquaporin 9 inhibits growth and metastasis of hepatocellular carcinoma cells via Wnt/β-catenin pathway

Liao

Chen

Liu

et al. 2020

Aging

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Hepatocellular carcinoma (HCC) is the most common type of liver cancer worldwide, and it is the second leading cause of cancer-related mortality. Aquaporin 9 (AQP9) is an essential aquaporin in the liver and located in the basolateral membrane of hepatocytes, but its roles on HCC has not been completely elucidated. This study investigated the regulatory functions of AQP9 in the pathogenesis of HCC. The expression levels of AQP9 were significantly down-regulated in HCC tissues and cells, which was also correlated with tumor size and number, TNM stage, five-year survival rate, lymphatic and distal metastasis within the patients. Furthermore, overexpressed AQP9 suppressed the proliferation, migration and invasion of HCC cells. The levels of PCNA, Ecad, N-cad, α-SMA, DVL2, GSK-3β, cyclinD1 and β-catenin in HCC cells were reduced by overexpressed AQP9, while cell apoptosis was remarkably enhanced. Additionally, following the treatment with Wnt/β-catenin signaling inhibitor (XAV939), the proliferative activity of HCC cells was significantly inhibited; PCNA and EMTrelated markers were down-regulated; migration and invasion of cells were notably suppressed; cell apoptotic rate was decreased. Vice versa, after the cells were treated with Wnt/β-catenin inducer (SKL2001), the effects caused by overexpressed AQP9 were abrogated. In vivo studies indicated that tumor volume and weight were remarkably decreased in AQP9 overexpression group, where the levels of Wnt/β-catenin signaling-and EMTassociated molecules were also reduced. Taken together, our results suggested that overexpressed AQP9 could inhibit growth and metastasis of HCC cells via Wnt/β-catenin pathway. AQP9 may be a promising therapeutic target for the treatment of patients with HCC.

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“…It has been reported that AQP9 is up-regulated in human glioma tissues [37]. In astrocytoma, AQP9 promotes cancer cell invasion and motility via the AKT pathway [38]. Ferreira et al suggested that CCL2 promoted the spread of oral cavity squamous cell carcinoma to lymph nodes and the macrophage in ltration might play a role in less aggressive behaviors [39].…”

Section: Discussionmentioning

confidence: 99%

Development of an immunogenomics-based prognostic index model of laryngeal squamous cell carcinoma

Shen

Zhou

Dong

et al. 2020

Preprint

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Background: The immune system greatly affects the prognosis of various malignancies. Studies on differentially expressed immune-related genes (IRGs) in the immune microenvironment of laryngeal squamous cell carcinoma (LSCC) have rarely been reported.Methods: In this paper, the prognostic potentials of IRGs in LSCC were explored. The RNAseq dataset containing differentially expressed IRGs and corresponding clinical information of LSCC patients was obtained from The Cancer Genome Atlas (TCGA). A total of 371 up-regulated and 61 down-regulated IRGs were identified. Subsequent functional enrichment analysis revealed that the pathway of IRGs was mainly enriched in the cytokine-cytokine receptor interaction. Then, 30 IRGs with prognostic potentials in LSCC were screened out, and the regulatory network induced by relevant transcription factors (TFs) were constructed.Results: Finally, multivariate Cox regression analysis was conducted to assess the prognostic potential of 15 IRGs after adjustment of clinical factors and LSCC patients were classified into 2 subgroups based on different outcomes. The gene expression of the model was verified by other independent databases. Nomogram including the 15 IRGs signature was established and shown some clinical net beneft. Intriguingly, B cells were significantly enriched in the low-risk group. Conclusion:These findings may contribute to the development of potential therapeutic targets and biomarkers for the new-immunotherapy of LSCC.

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AQP9 promotes astrocytoma cell invasion and motility via the AKT pathway

Cited by 16 publications

References 20 publications

Combined Systematic Review and Transcriptomic Analyses of Mammalian Aquaporin Classes 1 to 10 as Biomarkers and Prognostic Indicators in Diverse Cancers

Combined Systematic Review and Transcriptomic Analyses of Mammalian Aquaporin Classes 1 to 10 as Biomarkers and Prognostic Indicators in Diverse Cancers

Aquaporin 9 inhibits growth and metastasis of hepatocellular carcinoma cells via Wnt/β-catenin pathway

Development of an immunogenomics-based prognostic index model of laryngeal squamous cell carcinoma

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