Evaluation of the Mammalian Aquaporin Inhibitors Auphen and Z433927330 in Treating Breast Cancer
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA1134137 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR29764019_1.fastq.gz | Fastqsanger.gz | |||
| SRR29764019_2.fastq.gz | Fastqsanger.gz | |||
| SRR29764020_1.fastq.gz | Fastqsanger.gz | |||
| SRR29764020_2.fastq.gz | Fastqsanger.gz | |||
| SRR29764021_1.fastq.gz | Fastqsanger.gz |
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Similar Datasets
Project description:AQPs contribute to breast cancer progression and metastasis. We previously found that genetic inhibition of Aqp7 reduces primary tumor burden and metastasis in breast cancer. In this study, we utilized two AQP inhibitors, Auphen and Z433927330, to evaluate the efficacy of therapeutic inhibition of AQPs in breast cancer treatment. The inhibitors were evaluated in breast cancer for both cytotoxicity and in metabolic stability assays across both murine and human breast cancer cell lines. Both AQP inhibitors also affected expression of other AQP transcripts and proteins, which demonstrates compensatory regulation between AQP family members. As a single agent, Auphen treatment in vivo extended overall survival but did not impact primary or metastatic tumor burden. However, Auphen treatment made cells more responsive to chemotherapy (doxorubicin) or endocrine treatment (tamoxifen, fulvestrant). In fact, treatment with Tamoxifen reduced the overall AQP7 protein expression. RNA-Seq of breast cancer cells treated with Auphen identified mitochondrial metabolism genes as impacted by Auphen and may contribute to reducing mammary tumor progression, lung metastasis, and increased therapeutic efficacy of endocrine therapy in breast cancer. Interestingly, we found that Auphen and tamoxifen cooperate to reduce breast cancer cell viability, which suggests that Auphen treatment makes the cells more susceptible to Tamoxifen. Together, this study highlights AQPs as therapeutic vulnerabilities of breast cancer metastasis that are promising and should be exploited. However, the pharmacologic results suggest additional chemical refinements and optimization of AQP inhibition are needed to make these AQP inhibitors appropriate to use for therapeutic benefit in overcoming endocrine therapy resistance.
2024-08-01 | GSE271926 | GEO
Project description:AQPs contribute to breast cancer progression and metastasis. We previously found that genetic inhibition of Aqp7 reduces primary tumor burden and metastasis in breast cancer. In this study, we utilized two AQP inhibitors, Auphen and Z433927330, to evaluate the efficacy of therapeutic inhibition of AQPs in breast cancer treatment. The inhibitors were evaluated in breast cancer for both cytotoxicity and metabolic stability assays across both murine and human breast cancer cell lines. Both AQP inhibitors also affected the expression of other AQP transcripts and proteins, which demonstrates compensatory regulation between AQP family members. As a single agent, Auphen treatment in vivo extended overall survival but did not impact primary or metastatic tumor burden. However, Auphen treatment made cells more responsive to chemotherapy (doxorubicin) or endocrine treatment (tamoxifen, fulvestrant). In fact, treatment with Tamoxifen reduced overall AQP7 protein expression. RNA-seq of breast cancer cells treated with Auphen identified mitochondrial metabolism genes as impacted by Auphen and may contribute to reducing mammary tumor progression, lung metastasis, and increased therapeutic efficacy of endocrine therapy in breast cancer. Interestingly, we found that Auphen and tamoxifen cooperate to reduce breast cancer cell viability, which suggests that Auphen treatment makes the cells more susceptible to Tamoxifen. Together, this study highlights AQPs as therapeutic vulnerabilities of breast cancer metastasis that are promising and should be exploited. However, the pharmacologic results suggest additional chemical refinements and optimization of AQP inhibition are needed to make these AQP inhibitors appropriate to use for therapeutic benefit in overcoming endocrine therapy resistance.
| S-EPMC11311482 | biostudies-literature
Project description:Aquaporins (AQPs) are water channel proteins that are essential to life, being expressed in all kingdoms. In humans, there are 13 AQPs, at least one of which is found in every organ system. The structural biology of the AQP family is well-established and many functions for AQPs have been reported in health and disease. AQP expression is linked to numerous pathologies including tumor metastasis, fluid dysregulation, and traumatic injury. The targeted modulation of AQPs therefore presents an opportunity to develop novel treatments for diverse conditions. Various techniques such as video microscopy, light scattering and fluorescence quenching have been used to test putative AQP inhibitors in both AQP-expressing mammalian cells and heterologous expression systems. The inherent variability within these methods has caused discrepancy and many molecules that are inhibitory in one experimental system (such as tetraethylammonium, acetazolamide, and anti-epileptic drugs) have no activity in others. Some heavy metal ions (that would not be suitable for therapeutic use) and the compound, TGN-020, have been shown to inhibit some AQPs. Clinical trials for neuromyelitis optica treatments using anti-AQP4 IgG are in progress. However, these antibodies have no effect on water transport. More research to standardize high-throughput assays is required to identify AQP modulators for which there is an urgent and unmet clinical need.
| S-EPMC6480248 | biostudies-literature
Project description:Aquaporin-11 (AQP11), a new member of the aquaporin family, is localized in the endoplasmic reticulum (ER). Aqp11–/– mice neonatally suffer from polycystic kidneys derived from the proximal tubule. Its onset is proceeded by the vacuolization of ER. However, the mechanism for the formation of vacuoles and the development of cysts remain to be clarified. Here, we show that Aqp11–/– mice and polycystic kidney disease animals share a common pathogenic mechanism of cyst formation. Keywords: Geneexpression profile of Aqp11 knokout mouse kidney
2008-10-01 | GSE10634 | GEO
Project description:Mammalian microRNAs: Experimental evaluation of novel and previously annotated genes
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Project description:Malignant peripheral nerve sheath tumors (MPNSTs) are aggressive soft-tissue sarcomas which lack effective drugs. Previous studies support the usefulness of MEK inhibitors (MEKis) for treating RAS-driven tumors, however, the lack of preclinical assessment of MEK inhibitors in MPNSTs limit the clinical application as well as the development of combination therapy. In this study, we comprehensively evaluated 8 MEK inhibitors in terms of efficiency, safety and mechanisms of resistance for treating MPNSTs. We identified the most promising MEK inhibitor, trametinib, for the treatment of MPNSTs. Through high-throughput transcriptomic sequencing and drug screening, we discovered the upregulation of integrin signaling contributing to MEK inhibitor resistance, termed as cell adhesion-mediated drug resistance (CAM-DR). We also confirmed MET overactivation in MEKi-resistant MPNST cells. These targets are potential solutions to overcome MEKi- resistance in clinical applications.
2022-07-26 | GSE174100 | GEO
Project description:This experiment compared aRNA derived from the kidney inner medula of three mice lacking a functional aquaporin-1 gene to three wild type mice. Each sample was hybridized 4 times, against 4 of the other 5 samples, using an interwoven loop experimental design. Keywords: repeat sample
2004-05-05 | GSE1298 | GEO
Project description:The leaf transcriptome of the Arabidopsis thaliana aquaporin gene PIP1;2 T-DNA insertion line was compared to that of control plants. In total 730 genes were found to be differentially regulated. This regulation pattern was compared to mild drought stress and low CO2 Affymetrix data to elucidate whether loss of the aquaporin resembles transcriptomic changes of drought stress or lack of CO2 supply. Mild drought stress data were obtained from Harb A, Krishnan A, Ambavaram MMR, Pereira A (2010) Molecular and Physiological Analysis of Drought Stress in Arabidopsis Reveals Early Responses Leading to Acclimation in Plant Growth. Plant Physiology 154: 1254-1271 (GSE24177). Low CO2 data were obtained from Oliver E. Bläsing, Yves Gibon, Manuela Günther, Melanie Höhne, Rosa Morcuende, Daniel Osuna, Oliver Thimm, Björn Usadel, Wolf-Rüdiger Scheible, and Mark Stitt (2005) Sugars and Circadian Regulation Make Major Contributions to the Global Regulation of Diurnal Gene Expression in Arabidopsis. The Plant Cell, Vol. 17, 3257-3281 (GSE3423). 2 samples examined: wildtype and atpip1;2-1 mutant
2015-01-10 | E-GEOD-34984 | biostudies-arrayexpress
Project description:The leaf transcriptome of the Arabidopsis thaliana aquaporin gene PIP1;2 T-DNA insertion line was compared to that of control plants. In total 730 genes were found to be differentially regulated. This regulation pattern was compared to mild drought stress and low CO2 Affymetrix data to elucidate whether loss of the aquaporin resembles transcriptomic changes of drought stress or lack of CO2 supply. Mild drought stress data were obtained from Harb A, Krishnan A, Ambavaram MMR, Pereira A (2010) Molecular and Physiological Analysis of Drought Stress in Arabidopsis Reveals Early Responses Leading to Acclimation in Plant Growth. Plant Physiology 154: 1254-1271 (GSE24177). Low CO2 data were obtained from Oliver E. Bläsing, Yves Gibon, Manuela Günther, Melanie Höhne, Rosa Morcuende, Daniel Osuna, Oliver Thimm, Björn Usadel, Wolf-Rüdiger Scheible, and Mark Stitt (2005) Sugars and Circadian Regulation Make Major Contributions to the Global Regulation of Diurnal Gene Expression in Arabidopsis. The Plant Cell, Vol. 17, 3257-3281 (GSE3423).
2015-01-10 | GSE34984 | GEO
Project description:To investigate the expression of aquaporin gene family under high temperature stress
2022-06-28 | GSE206791 | GEO