Autocrine Motility Factor Modulates Proliferation Signaling Mediated By GPER
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA471076 | ENA |
REPOSITORIES: ENA
Similar Datasets
Project description:Traditional surgery plus radiotherapy or chemotherapy, existing targeted therapies failed to significantly improve the survival rate of recurrent endometrial cancer, so suggesting that mechanism of recurrence and progression that modulates in endometrial cancer is clinically important. Here, we show that GPER(G protein-coupled estrogen receptor 1) was binded to AMF, and the complex were translocation form plasma to cytoplasmic. Mechanistic investigations elucidated that interaction of AMF with GPER triggers phosphoinositide-3-kinase (PI3K) signaling activating and accelerating the ability of endometrial cancer cells growth. Furthermore, we found that AMF may contribute to GPER-mediated endometrial cancer progression using animal experiments and human histological experiments which be consistent with the above conclusions. On the basis of these evidences including invivo and invitro, our findings suggest that AMF–GPER interaction might be novel key molecular targets for therapeutic management of patients with endometrial cancer, whose disease were progression and recurrence.
2019-03-19 | GSE114362 | GEO
Project description:Traditional surgery plus radiotherapy or chemotherapy, existing targeted therapies failed to significantly improve the survival rate of recurrent endometrial cancer, so suggesting that mechanism of recurrence and progression that modulates in endometrial cancer is clinically important. Here, we show that GPER(G protein-coupled estrogen receptor 1) was binded to AMF, and the complex were translocation form plasma to cytoplasmic. Mechanistic investigations elucidated that interaction of AMF with GPER triggers phosphoinositide-3-kinase (PI3K) signaling activating and accelerating the ability of endometrial cancer cells growth. Furthermore, we found that AMF may contribute to GPER-mediated endometrial cancer progression using animal experiments and human histological experiments which be consistent with the above conclusions. On the basis of these evidences including invivo and invitro, our findings suggest that AMF–GPER interaction might be novel key molecular targets for therapeutic management of patients with endometrial cancer, whose disease were progression and recurrence.
2019-03-12 | PXD009780 | Pride
Project description:Introduction: Type 1 diabetes (T1D) significantly affects gastrointestinal (GI) motility and contributes to complications, such as gastroparesis, constipation, and fecal incontinence. Notably, these complications have a higher prevalence in female patients, underscoring a critical knowledge gap in the understanding of the underlying mechanisms. Given the emerging role of the G-protein-coupled estrogen receptor (GPER) in GI motility regulation, our study investigated the potential contribution of diabetes-induced changes in GPER expression to pathophysiology. Hypothesis: We hypothesized that diabetes-induced perturbations in GPER expression contribute to pathophysiological mechanisms affecting GI motility in T1D, with notable sex-dependent variations. Methods: we assessed GPER mRNA and protein expression levels using quantitative reverse-transcription PCR and western blot analyses, and quantified the changes in nuclear DNA methyltransferases and histone modifications (H3K4Me3, H3Ac, and H3K27Ac) were quantified using ELISA kits. Targeted bisulfite and chromatin immunoprecipitation sequencing were used to evaluate DNA methylation and histone modifications around the GPER promoter by chromatin immunoprecipitation assays in gastric and colonic smooth muscle tissues of male and female control (CTR) and non-obese diabetic (NOD) mice. Results: Our results revealed significant downregulation of GPER in NOD mice, with marked sex-dependent variations. Mechanistically, this downregulation was associated with reduced H3K4me3, H3ac, and H3K27ac levels in NOD male gastric smooth muscle. In contrast, downregulation in female gastric smooth muscle cells has been linked to decreased H3K4me3 and H3ac levels. Male NOD colonic smooth muscle exhibited elevated H3ac and H3K27ac levels, whereas female NOD colonic smooth muscle demonstrated diminished enrichment of H3ac and H3K27ac at the GPER promoter. Additionally, DNA methylation is elevated in NOD male colonic smooth muscle compared to NOD females. Conclusion: Our findings elucidate sex-specific epigenetic mechanisms contributing to T1D-mediated suppression of GPER expression in the gastrointestinal tract. These insights not only advance our understanding of T1D complications but also suggest promising avenues for targeted therapeutic interventions.
2024-05-29 | GSE255236 | GEO
Project description:BackgroundAutocrine motility factor (AMF) is a critical factor regulating aggressiveness of endometrial cancer (EC). Multiple pieces of evidence indicate that it is through G protein coupled estrogen receptor (GPER) signaling pathway that some growth factors promoted the migration and proliferation of tumor cells. The aim of this study is to explore the role of GPER-1 in AMF mediated regulatory mechanisms of EC recurrence and progression.MethodsReal-Time Cell Analysis (RTCA) assays were performed to assess whether AMF depends on Autocrine motility factor recepter (AMFR) signaling in EC cells. A genome-wide expression microarray and Yeast Two-Hybrid assay were used to detect AMF and GPER-1 interaction in the context of AMFR depletion, and co-immunoprecipitation and immunofluorescence experiments were performed to confirm the physical interaction. Isobaric Tags for Relative and Absolute Quantification (iTRAQ) analysis was used for the identification of the target pathway activated by AMF-GPER-1 interaction. Cohorts of mice harboring xenografts derived from modified SPEC2 cell lines were treated with or without exogenous AMF to validate the results of previous experiments. Immunohistochemistry was performed to assess AMF and GPER-1 expression in endometrial cancer specimens and normal endometrium.ResultsOur data showed that GPER-1 binds to AMF and the formed complex translocates from the plasma membrane to the cytoplasm. Mechanistic investigations demonstrated that interaction between AMF and GPER-1 triggers phosphoinositide-3-kinase signaling and promotes EC cell growth. More importantly, through animal experiments and human tissue experiments, we found that AMF contributes to GPER-1-mediated EC progression, which is consistent with the above observations.ConclusionsOur work not only delineated the regulatory mechanisms of endometrial cancer progression by AMF-GPER-1-AKT signaling cascade but also laid the foundation of targeting this pathway for treating endometrial cancer.
| S-EPMC6402158 | biostudies-literature
Project description:Histone deacetylase inhibitors impair glioblastoma cell motility and proliferation
| PRJNA789840 | ENA
Project description:Type 2 diabetes mellitus (T2DM) causes gastroparesis, delayed intestinal transit, and constipation, for unknown reasons. Complications are predominant in men and postmenopausal women, suggesting a female hormone-mediated mechanism. Low G-protein coupled estrogen receptor (GPER) expression from epigenetic modifications may explain it. We explored sexually differentiated GPER expression and gastrointestinal symptoms related to GPER alterations in wild-type (WT) and T2DM mice (db/db). GPER mRNA and protein expression, DNA methylation and histone modifications were measured from stomach and colon samples of db/db and WT mice. We found that WT female tissues have the highest GPER mRNA and protein expressions. The expression is lowest in all db/db. The lowest mRNA levels are in the male stomach and female colon. GPER downregulation is associated with promoter hypermethylation and reduced enrichment of H3K4me3 and H3K27ac marks around the GPER promoter. T2DM impairs gut GPER expression, and epigenetic sex-specific mechanisms matter in the downregulation.
2023-12-15 | GSE240515 | GEO
Project description:Autocrine motility factor (AMF) enhances invasion by breast cancer cells, but how its secretion and effector signaling are controlled in the tumor microenvironment is not fully understood. In this study, we investigated these issues with a chimeric AMF that is secreted at high levels through a canonical endoplasmic reticulum (ER)/Golgi pathway. Using this tool, we found that AMF enhances tumor cell motility by activating AKT/ERK, altering actin organization, and stimulating β-catenin/TCF and activating protein 1 transcription. EGF enhanced secretion of AMF through its casein kinase II-mediated phosphorylation. RNA interference-mediated attenuation of AMF expression inhibited EGF-induced invasion by suppressing extracellular signal-regulated kinase signaling. Conversely, exogenous AMF overcame the inhibitory effect of EGF receptor inhibitor gefitinib on invasive motility by activating HER2 signaling. Taken together, our findings show how AMF modulates EGF-induced invasion while affecting acquired resistance to cytotoxic drugs in the tumor microenvironment.
| S-EPMC4091754 | biostudies-literature
Project description:MicroRNAs are widely expressed in the normal pubertal mammary gland and orchestrate mammary gland development by regulating cell proliferation, differentiation, apoptosis, and metabolism. Although human Growth hormone(hGH) plays fundamental roles in normal mammary gland development and elevated autocrine hGH levels have been documented to contribute to breast cancer, whether hGH should influence the expression pattern and the functional roles of miRNAs in this context remain unknown.This study explores the effects of autocrine hGH on microRNA expression in MCF7 cell.
2014-12-31 | GSE58845 | GEO
Project description:The matricellular protein Fibulin-5 regulates β-cell proliferation in an autocrine/paracrine manner
| PRJNA601160 | ENA
Project description:MEOX2-mediated regulation of Cathepsin S promotes cell proliferation and motility in glioma.
| PRJNA812002 | ENA