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The phosphate exporter XPR1/SLC53A1 is required for the tumorigenicity of ovarian cancer.

ABSTRACT: The phosphate exporter XPR1/SLC53A1 is required for the tumorigenicity of ovarian cancer.

PROVIDER: PRJNA783541 | ENA |

REPOSITORIES: ENA

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The phosphate exporter XPR1/SLC53A1 is required for the tumorigenicity of ovarian cancer.

Project description:Ovarian cancer is the fifth cause of cancer-related death in women. Ovarian clear cell carcinoma (OCCC) is a chemotherapy-resistant epithelial ovarian cancer with poor prognosis. As a basis for the development of therapeutic agents that may improve the prognosis of OCCC, we performed a screen for proteins critical for the tumorigenicity of OCCC using the CRISPR/Cas9 system. Here we show that knockdown of the phosphate exporter XPR1/SLC53A1 induces the growth arrest and apoptosis of OCCC cells in vitro. Moreover, we demonstrate that knockdown of XPR1/SLC53A1 inhibits the proliferation of OCCC cells xenografted into immunocompromised mice. These results suggest that XPR1/SLC53A1 plays a critical role in the tumorigenesis of OCCC cells. We speculate that XPR1/SLC53A1 might be a promising molecular target for the therapeutic treatment of OCCC.

2022-07-07 | GSE189552 | GEO

MSC stimulate ovarian tumor growth during intercellular communication but reduce tumorigenicity after fusion with ovarian cancer cells

Project description:MSC stimulate ovarian tumor growth during intercellular communication but reduce tumorigenicity after fusion with ovarian cancer cells

| PRJNA482005 | ENA

Mycobacterium tuberculosis Phosphate Uptake System Component PstA2 is Not Required for Gene Regulation or Virulence

Project description:The Mycobacterium tuberculosis genome encodes two complete high-affinity Pst phosphate-specific transporters. We previously demonstrated that a membrane-spanning component of one Pst system, PstA1, was essential both for M. tuberculosis virulence and for regulation of gene expression in response to external phosphate availability. To determine if the alternative Pst system is similarly required for virulence or gene regulation, we constructed a deletion of pstA2. Transcriptome analysis revealed that PstA2 is not required for regulation of gene expression in phosphate-replete growth conditions. PstA2 was also dispensable for replication and virulence of M. tuberculosis in a mouse aerosol infection model. However, a ∆pstA1∆pstA2 double mutant was attenuated in mice lacking the cytokine interferon-gamma, suggesting that M. tuberculosis requires high-affinity phosphate transport to survive phosphate limitation encountered in the host. Surprisingly, ∆pstA2 bacteria were more resistant to acid stress in vitro. This phenotype is intrinsic to the alternative Pst transporter since a ∆pstS1 mutant exhibited similar acid resistance. Our data indicate that the two M. tuberculosis Pst transporters have distinct physiological functions, with the PstA1 transporter being specifically involved in phosphate sensing and gene regulation while the PstA2 transporter influences survival in acidic conditions.

2016-06-29 | GSE83812 | GEO

Mycobacterium tuberculosis Phosphate Uptake System Component PstA2 is Not Required for Gene Regulation or Virulence

Project description:The Mycobacterium tuberculosis genome encodes two complete high-affinity Pst phosphate-specific transporters. We previously demonstrated that a membrane-spanning component of one Pst system, PstA1, was essential both for M. tuberculosis virulence and for regulation of gene expression in response to external phosphate availability. To determine if the alternative Pst system is similarly required for virulence or gene regulation, we constructed a deletion of pstA2. Transcriptome analysis revealed that PstA2 is not required for regulation of gene expression in phosphate-replete growth conditions. PstA2 was also dispensable for replication and virulence of M. tuberculosis in a mouse aerosol infection model. However, a âpstA1âpstA2 double mutant was attenuated in mice lacking the cytokine interferon-gamma, suggesting that M. tuberculosis requires high-affinity phosphate transport to survive phosphate limitation encountered in the host. Surprisingly, âpstA2 bacteria were more resistant to acid stress in vitro. This phenotype is intrinsic to the alternative Pst transporter since a âpstS1 mutant exhibited similar acid resistance. Our data indicate that the two M. tuberculosis Pst transporters have distinct physiological functions, with the PstA1 transporter being specifically involved in phosphate sensing and gene regulation while the PstA2 transporter influences survival in acidic conditions. Aerobically growing logarithmic phase Wt or pstA2 mutant or pstA1A2 double mutant strains were grown in phosphate replete media and analyzed after several hours. Experiments were repeated in triplicate.

2016-06-29 | E-GEOD-83812 | biostudies-arrayexpress

MSC stimulate ovarian tumor growth during intercellular communication but reduce tumorigenicity after fusion with ovarian cancer cells

Project description:Functional changes were investigated in vitro and in vivo following spontaneous fusion and hybrid cell formation in co-cultures of primary human mesenchymal stroma/stem-like cells (MSC) with human SK-OV-3 ovarian cancer cells. Lentiviral fluorescence-labeled MSC with eGFP and ovarian cancer cells labeled with mcherry resulted in dual-fluorescing hybrid cells. Double FACS sorting and single cell cloning revealed two different aneuploid hybrid populations (SK-hyb1 and SK-hyb2)

2018-10-29 | GSE117411 | GEO

Gene expression profiling of epithelial ovarian cancer by bulk RNA-seq

Project description:Ovarian cancer has one of the worst prognoses among gynecologic malignancies. About 60% of ovarian cancer cases are diagnosed at Stages III and IV, and their five-year survival rate is less than 30%. Ovarian cancer is classified into four major histological subtypes; serous, clear cell, endometrioid and mucinous. Ovarian clear cell carcinoma (OCCC) is less sensitive to conventional platinum-based chemotherapy and has worse prognosis than other subtypes. In this study, we attempted to identify novel molecular targets critical for the proliferation and tumorigenicity of OCCC using the CRISPR/Cas9 system, and identified some genes as important candidates. Some of these candedates were upregulated in ovarian cancer tissue, especially OCCC. Our results suggest that not only may be these candedates a promising diagnostic maker for OCCC, drugs against these candedates would be useful for the therapeutic treatment of OCCC.

2022-06-08 | GSE189553 | GEO

ARHGAP10, downregulated in ovarian cancer, suppresses tumorigenicity of ovarian cancer cells.

Project description: Not available

| S-EPMC4823924 | biostudies-literature

PRC1-mediated epigenetic programming is required to generate the ovarian reserve

Project description:The ovarian reserve defines the female reproductive lifespan, which in humans spans decades due to robust maintenance of meiotic arrest in oocytes residing in primordial follicles. Epigenetic reprogramming, including DNA demethylation, accompanies meiotic entry, but the chromatin changes that underpin the generation and preservation of ovarian reserves are poorly defined. We report that the Polycomb Repressive Complex 1 (PRC1) establishes repressive chromatin states in perinatal mouse oocytes that directly suppress the gene expression program of meiotic prophase-I and thereby enable the transition to dictyate arrest. PRC1 dysfuction causes depletion of the ovarian reserve and leads to premature ovarian failure. Our study demonstrates a fundamental role for PRC1-mediated gene silencing in female reproductive lifespan, and reveals a critical window of epigenetic programming required to establish ovarian reserve.

2022-06-26 | GSE184208 | GEO

Ovarian serous cancer

Project description:Ovarian serous cancer

| PRJNA117359 | ENA

High concentration of prolactin induce oxidative stress in ovine ovarian GCs by the pentose phosphate pathway through regulating the ROS and mitophagy pathways

Project description:High concentration of prolactin induce oxidative stress in ovine ovarian GCs by the pentose phosphate pathway through regulating the ROS and mitophagy pathways.

2022-10-23 | PXD037645 | iProX

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