|CSC-DC000807||Panoply™ Human AQP1 Knockdown Stable Cell Line||Inquiry|
|CSC-SC000807||Panoply™ Human AQP1 Over-expressing Stable Cell Line||Inquiry|
|AD01211Z||Human AQP1 adenoviral particles||Inquiry|
|LV05270L||human AQP1 (NM_001185061) lentivirus particles||Inquiry|
|LV05271L||human AQP1 (NM_198098) lentivirus particles||Inquiry|
|LV05272L||human AQP1 (NM_001185062) lentivirus particles||Inquiry|
|LV05273L||human AQP1 (NM_001185060) lentivirus particles||Inquiry|
|CDCB159436||Human AQP1 ORF clone (BC022486)||Inquiry|
|CDCB163804||Chicken AQP1 ORF Clone (NM_001039453)||Inquiry|
|CDCB180557||Rabbit AQP1 ORF clone (XM_002713737.2)||Inquiry|
|CDCR029132||Human AQP1 ORF clone (NM_001185061.1)||Inquiry|
|CDCR029134||Human AQP1 ORF clone (NM_001185060.1)||Inquiry|
|CDCR029136||Human AQP1 ORF clone (NM_001185062.1)||Inquiry|
|CDCR377638||Rat Aqp1 ORF Clone(NM_012778.1)||Inquiry|
|CDCS409176||Human AQP1 ORF Clone (BC022486)||Inquiry|
|CDFH001007||Human AQP1 cDNA Clone(NM_001185060.1)||Inquiry|
|CDFH001008||Human AQP1 cDNA Clone(NM_001185062.1)||Inquiry|
|CDFH001009||Human AQP1 cDNA Clone(NM_001185061.1)||Inquiry|
|CDFR010580||Rat Aqp1 cDNA Clone(NM_012778.1)||Inquiry|
|MiUTR1M-01602||AQP1 miRNA 3'UTR clone||Inquiry|
|MiUTR1R-00318||AQP1 miRNA 3'UTR clone||Inquiry|
|MiUTR3H-00191||AQP1 miRNA 3'UTR clone||Inquiry|
|SHG066581||shRNA set against Mouse Aqp1(NM_007472.2)||Inquiry|
|SHG066635||shRNA set against Rat Aqp1(NM_012778.1)||Inquiry|
|SHH238798||shRNA set against Human AQP1 (NM_198098.2)||Inquiry|
|SHH238802||shRNA set against Mouse AQP1 (NM_007472.2)||Inquiry|
|SHH238806||shRNA set against Rat AQP1 (NM_012778.1)||Inquiry|
|SHW002329||shRNA set against Chicken AQP1 (NM_001039453)||Inquiry|
AQP1 (aquaporin 1) is aquaporin 1. The human AQP1 gene is located on chromosome 7p14 and contains four exons and three introns. AQP1 is a transmembrane tetramer whose monomer has a molecular mass of approximately 28 kDa. AQP1 is currently the most studied aquaporin. AQP1 mainly mediates the transport of water molecules, and also transports some cations across the membrane to participate in the cell migration process. In the human body, AQP1 is mainly distributed in the tissue epithelial barrier associated with fluid flow, such as the proximal convoluted tubules, choroid plexus, peripheral microvessels, dorsal root ganglia, ciliary epithelium and trabecular meshwork. AQP1 is involved in a series of physiological activities such as urine collection, aqueous humor and cerebrospinal fluid production, salivation, and neuronal signal transduction. It also enhances the mechanical compliance of cells under external changes and participates in axonal regeneration, angiogenesis, injury repair and mediate exocytosis.
Ion channels and transporters (ICTs) play an important role in tumor progression. As a typical ICT, AQP1 is capable of transporting water molecules and some cations. Overexpression of AQP1 affects cell migration, proliferation, and angiogenesis by altering cell volume, adjusting cell membrane potential, and activating a series of downstream signaling pathways to promote tumor progression.
There is currently much evidence that overexpression or underexpression of AQP1 significantly affects cell migration. In the mouse melanoma B16F10 cell line cultured in vitro and the mouse breast cancer 4T1 cell line, AQP1 expression accelerated the migration of these cells, and the polar expression of AQP1 was found in the migration direction of the migrated cells. Studies have also found that overexpression of AQP1 promotes the migration of bone marrow mesenchymal stem cells (MSCs) in vitro. Decreasing AQP1 expression inhibits MSC migration. The researchers injected green fluorescent protein (GFP)-labeled AQP1 overexpressing MSC into rats with femoral fractures, and found that the fluorescence intensity of the fracture site was significantly higher than that of the control group. This significant association of AQP1 with cell migration suggests that AQP1 may play an important role in cancer metastasis and invasion.
Tumor growth and spread are largely dependent on tumor angiogenesis leading to vascularization of the tumor stroma. Nicchia et al. knocked down AQP1 in mice with siRNA and subcutaneously implanted B16F10 melanoma cells. It was found that inhibition of AQP1 expression reduced tumor microvessel density. Esteva-Font et al. also found that AQP1 deficiency in mouse mammary tumour virus-driven polyoma virus middle T oncogene (MMTVPyVT) mice can reduce the density of tumor microvessels. Vascular endothelial growth factor (VEGF) is a key molecule that promotes angiogenesis. Studies have found that AQP1 is positively correlated with the density of microvessels in the tumor during the progression of endometrial adenocarcinoma. The ratio of AQP1 to intratumoral microvessel density was also positively correlated with VEGF expression. This suggests that AQP1 may interact with VEGF for angiogenesis.
Tumor Cell Proliferation
AQP1 is involved in tumor cell proliferation through a variety of mechanisms. Studies have shown that AQP1 is overexpressed in the mouse embryonic fibroblast cell line NIH-3T3 cultured in vitro and found to promote tumor cell proliferation. After shRNA down-regulation of AQP1 expression in two osteosarcoma cell lines U2OS and MG63, tumor proliferation was found to be significantly inhibited. The primary malignant mesothelioma cells obtained by Klebe et al. in pleural effusion were knocked down by AQP1 inhibitor AqB050 or siRNA, and the proliferation of tumor cells was found to be inhibited. This shows that AQP1 has a significant effect on tumor proliferation.
Cell proliferation is closely related to changes in cell volume. During the cell cycle, as the protein is synthesized and DNA is replicated, the cell volume increases. Galáncobo et al. found that AQP1 overexpression can increase the permeability of hydrogen peroxide and regulate protein expression related to cell proliferation. At the same time, its cell volume is larger than normal cells, suggesting that AQP1 may promote tumor proliferation by increasing cell volume.
Downstream Signal Path
In addition to changing cell volume and regulating cell membrane potential, AQP1 also activates a series of downstream signal transduction pathways by interacting with other membrane proteins or transcription factors to promote tumor progression. The Wnt pathway is a kind of evolutionarily highly conserved signaling pathway that plays an important role in the early development of embryos, growth metabolism and tissue regeneration. β-Catenin is a key protein in the Wnt signaling pathway, and Wnt signaling can inhibit the degradation of β-catenin and stabilize the level of β-catenin in the cytoplasm, thereby regulating gene expression. Meng et al. found co-immunoprecipitation of AQP1 and β-catenin in mesenchymal stem cell MSCs with high expression of AQP1, accompanied by up-regulation of β-catenin expression. Yun et al. found that elevated expression of β-catenin in pulmonary muscle cells is associated with the C-terminal tail of AQP1 containing a protein-binding site. The binding of the C-terminus of AQP1 to β-catenin blocks the binding of β-catenin to the Axin/APC/GSK3 complex and inhibits the degradation of β-catenin.
Figure 1. Proposed interaction of AQP1 with Wnt/ β-catenin signalling and cadherin-catenin complex. (Tomita, et al. 2017).
FAK is a cytoplasmic tyrosine kinase that mediates growth factor receptor and integrin-mediated signal transduction. FAK enhances the migration of tumor cells, promotes EMT and tumor angiogenesis, thereby promoting tumor progression. Meng et al. found a phenomenon in which FAK co-precipitated with AQP1 and β-catenin in AQP1 overexpressing mesenchymal stem cells, suggesting that FAK may form a complex with AQP1, β-catenin and Lin-7. At the same time, the knockout of FAK attenuated the promotion of AQP1 on MSC cell migration. Overexpression of AQP1 has no effect on FAK mRNA levels, so up-regulation of FAK expression is thought to occur at post-translational levels.
Hypoxia Promotes Up-regulation of AQP1 Expression
Hypoxia is a common feature of different types of cancer cells due to the rapid proliferation of cells. And hypoxia will further promote tumor proliferation. The significance of up-regulation of AQP1 expression in response to treatment is that anaerobic glycolysis is enhanced by hypoxia, intracellular lactic acid is accumulated, pH is lowered, and cells need to transport H+ to the outside of the cell. However, this process is related to the reaction of H+ with HCO3− catalyzed by carbonic anhydrase in the cytoplasm, and the produced water molecules are transported outside the cell by AQP1 to avoid excessive edema. Therefore, the relationship between AQP1 and tumors can be considered as a kind of positive feedback to some extent, that is, the rapid proliferation of cells leads to the cells in an oxygen-deficient environment. The expression of AQP1 is up-regulated by hypoglycemia and increased expression of HIF. Then, overexpression of AQP1 further aggravates cell migration by altering cell morphology and activating a series of downstream signal transduction pathways, finally it can intensify the process of cell migration, proliferation and angiogenesis, and promote tumor progression.
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