P120 RasGAP and ZO-2 promote the tumor suppressor function of p190A RhoGAP
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA876272 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR21404570.fastq.gz | Fastqsanger.gz | |||
| SRR21404571.fastq.gz | Fastqsanger.gz | |||
| SRR21404572.fastq.gz | Fastqsanger.gz | |||
| SRR21404573.fastq.gz | Fastqsanger.gz | |||
| SRR21404574.fastq.gz | Fastqsanger.gz |
Items per page: 5 1 - 5 of 24 |
Similar Datasets
Project description:ARHGAP35 encoding p190A RhoGAP (p190A) was identified by GWAS as a major human cancer gene. Our published studies have determined that p190A is a tumor suppressor that activates the canonical Hippo pathway. To elucidate how p190A signals in this context, we performed mass spectrometry to identify p190A binding proteins. Two interactors were identified significantly more frequently than others: p120 RasGAP (p120) and ZO-1. Originally p190A was cloned via its direct binding to p120, hence validating our approach. In addition, we found that p190A also binds to ZO-2. The interaction of p190A with ZO-2 is dependent on p120, thus suggesting formation of a ternary complex. Next, we determine that both p120 and ZO-2, but not ZO-1, are necessary for p190A to activate LATS kinases and suppress tumorigenesis in a xenograft mouse model. Moreover, the interactions with p120 and ZO-2 are essential for transcriptional modulation by p190A, including the CDH1 gene encoding E-cadherin, which we previously have demonstrated is essential for p190A signaling. Collectively, this work identifies a novel tumor suppressor interactome of p190A, which includes ZO-2, an established constituent of the Hippo pathway, and p120, which in spite of its strong association with Ras signaling, is essential for p190A to activate LATS kinases.
2023-04-15 | GSE212619 | GEO
Project description:Myeloid-derived suppressor cells promote lung cancer metastasis
| PRJNA564103 | ENA
Project description:Chlamydia psittaci Zo Pa raw sequence reads
| PRJNA312240 | ENA
Project description:ZO-1 immunoprecipitation samples from BAECs, treated or not with VEGF, were analyzed using LC-MS/MS.
2024-05-22 | PXD029332 | Pride
Project description:Myeloid-derived suppressor cells (MDSC) represent a heterogeneous population of immature myeloid cells that accumulate in blood, liver, spleen and tumors upon chronic inflammation and tumor development in patients and mice. Acute hepatitis is characterized by a fast infiltration of inflammatory cells in the liver and increased enzymatic activity at this organ that could lead into liver fibrosis and cirrhosis. We have studied the biology of hepatic MDSC in acute hepatitis. Unexpectedly, hepatic MDSC, which accumulate in the liver of mice bearing subcutaneous tumors, failed to suppress inflammatory responses upon Con A injection, but instead were responsible for exacerbating acute liver damage. Phenotypic, genetic and functional studies demonstrated rapid changes of hepatic MDSC from a suppressor phenotype into a pro-inflammatory subset as early as 3 hours after Con A injection. An increase in the expression of pro-inflammatory cytokines, costimulatory molecules such as CD80, CD86 and CD40 along with a loss of suppressor function was noticed in mice upon Con A treatment. These changes were CD40-dependent and not found in CD40-/- MDSC. Interestingly, CD40 ligation of human MDSC in vitro resulted in down-regulation of arginase I expression and suppressor function. Finally, blockade of ROS production in hepatic MDSC ameliorated hepatocyte damage suggesting that MDSC mediated toxicity was ROS dependent. We believe that these findings reflect how MDSC plasticity can be modulated to promote inflammation, opening a new path for therapies targeting innate suppressive cells in cancer patients. EL4 tumors were established in C57BL/6 mice, then mice were injected either with PBS (n=3) or 12.5mg/kg Con A (n=3). Three hours later mice were sacrificed, liver CD11b+Gr-1+ cells were sorted and samples were processed for gene expression analysis.
2015-09-01 | E-GEOD-50949 | biostudies-arrayexpress
Project description:SHED-exos can ameliorate Sjögren syndrome-induced hyposalivation through miRNAs mediated Akt/Slug/ZO-1 expression.
2022-04-01 | GSE199497 | GEO
Project description:Myeloid-derived suppressor cells (MDSCs) suppress antitumor immune activities and facilitate cancer progression. Although the concept of immunosuppressive MDSCs is well established, the mechanism that MDSCs regulate non-small cell lung cancer (NSCLC) progression through the paracrine signals is still lacking. Here, we reported that the infiltration of MDSCs within NSCLC tissues were associated with the progression of cancer status, and were positively correlated with the Patient-derived xenograft (PDX) model establishment, and poor patient prognosis. Intratumoral MDSCs directly promoted NSCLC metastasis and highly expressed chemokines that promote NSCLC cells invasion, including CCL11. CCL11 was capable of activating the AKT and ERK signaling pathways to promote NSCLC metastasis through the epithelial-mesenchymal transition (EMT) process. Moreover, high expression of CCL11 was associated with a poor prognosis in lung cancer as well as other types of cancer. Our findings underscore that MDSCs produce CCL11 to promote NSCLC metastasis via activation of ERK and AKT signaling and induction of EMT, suggesting that the MDSCs-CCL11-ERK/AKT-EMT axis contains potential targets for NSCLC metastasis treatment.
2021-01-17 | GSE136949 | GEO
Project description:Myeloid-derived suppressor cells (MDSC) represent a heterogeneous population of immature myeloid cells that accumulate in blood, liver, spleen and tumors upon chronic inflammation and tumor development in patients and mice. Acute hepatitis is characterized by a fast infiltration of inflammatory cells in the liver and increased enzymatic activity at this organ that could lead into liver fibrosis and cirrhosis. We have studied the biology of hepatic MDSC in acute hepatitis. Unexpectedly, hepatic MDSC, which accumulate in the liver of mice bearing subcutaneous tumors, failed to suppress inflammatory responses upon Con A injection, but instead were responsible for exacerbating acute liver damage. Phenotypic, genetic and functional studies demonstrated rapid changes of hepatic MDSC from a suppressor phenotype into a pro-inflammatory subset as early as 3 hours after Con A injection. An increase in the expression of pro-inflammatory cytokines, costimulatory molecules such as CD80, CD86 and CD40 along with a loss of suppressor function was noticed in mice upon Con A treatment. These changes were CD40-dependent and not found in CD40-/- MDSC. Interestingly, CD40 ligation of human MDSC in vitro resulted in down-regulation of arginase I expression and suppressor function. Finally, blockade of ROS production in hepatic MDSC ameliorated hepatocyte damage suggesting that MDSC mediated toxicity was ROS dependent. We believe that these findings reflect how MDSC plasticity can be modulated to promote inflammation, opening a new path for therapies targeting innate suppressive cells in cancer patients.
2015-09-01 | GSE50949 | GEO
Project description:Recently, ARHGAP35 encoding p190A RhoGAP was unexpectedly found to rank among the 20-30 most frequently mutated genes in human cancer. The spectrum of mutations in ARHGAP35 is consistent with that of a tumor suppressor, but the underlying mechanisms are not well understood. In this work we sought to elucidate functions for p190A RhoGAP (p190A) and its isoform p190B RhoGAP (p190B) that might confer tumor suppressor capacities in epithelial cells. We establish an essential role for p190A and p190B to mediate contact inhibition of cell proliferation (CIP). Both p190A and p190B localize in part to adherens junctions, which is consistent with a role in CIP. Using an unbiased approach, we determine that p190A and p190B repress expression of a cassette of genes that are modulated by the Hippo pathway. Moreover, we demonstrate that p190A and p190B promote activation of LATS kinases and inhibit translocation of the Hippo transducer YAP to the nucleus. Next, we validate that expression of an activated form of YAP induces a gene signature with significant similarities to that of cells depleted of p190A and p190B expression. Furthermore, we establish that p190A and p190B promote CIP by repressing YAP-TEAD-mediated gene transcription. Collectively, our results demonstrate that p190 RhoGAPs serve as activators of the Hippo pathway, which is widely implicated in CIP. Our work suggests that ARHGAP35 belongs to group of tumor suppressor genes, including AJUBA, CDH1, and NF2, with gene products that localize to cell-cell junctions and modulate the activity MST/LATS complex.
2016-12-30 | GSE75099 | GEO
Project description:Muscicapa striata striata isolate:MNHN ZO 2018-449 Genome sequencing and assembly
| PRJNA936819 | ENA