| http://purl.uniprot.org/citations/35541901 | http://www.w3.org/1999/02/22-rdf-syntax-ns#type | http://purl.uniprot.org/core/Journal_Citation |
| http://purl.uniprot.org/citations/35541901 | http://www.w3.org/2000/01/rdf-schema#comment | "Background: Control of ER-mitochondrial Ca2+ fluxes is a critical checkpoint to determine cell fate under stress. The 75-kDa glucose-regulated protein (GRP75) is a key tether protein facilitating mitochondria-associated ER membrane (MAM) formation through the IP3R-GRP75-VDAC1 complex. Although GRP75 contributes to cisplatin (CP)-resistance of ovarian cancer (OC), the underlying mechanisms are not clear. Methods: CP-resistant and -sensitive OC cell lines with GRP75 stable modulation were established. Confocal, PLA, co-IP, and TEM analysis were utilized to detect MAM integrity. Live cell Ca2+ imaging, intracellular ATP, ROS, and NAD+ assays were utilized to investigate ER-to-mitochondrial Ca2+ transfer and mitochondrial bioenergetics. Western blot, flow cytometry, CCK-8, Δψm, and mPTP assays were utilized to examine apoptotic cell death. Bioinformatics, patient's specimens, and immunohistochemistry were conducted to obtain the clinical relevance for GRP75-facilitated MAM formation. Results: GRP75-faciliated MAM formation was enriched in CP-resistant OC cells. CP-exposure only increased MAM formation in CP-sensitive OC cells, and enrichment of GRP75 and VDAC1 at MAMs is indispensable to CP-resistance. Diminishing MAM integrity by GRP75-deficiency reduced ER-to-mitochondria Ca2+ transfer, accelerated CP-induced mitochondrial dysfunction, provoked catastrophic ROS, and enhanced CP-triggered apoptotic cell death in OC cells. Clinical investigations confirmed the enrichment of GRP75-faciliated MAM formation in relapsed OC patients, and such enrichment was associated with the CP-resistance phenotype. Conclusion: GRP75-overexpression confers CP-resistance by distinctively managing MAM-facilitated Ca2+ fluxes and the pro-survival ROS signal, whereas GRP75-deficiency induces cell death via bioenergetic crisis and apoptotic ROS accumulation in OC cells. Our results show that GRP75-faciliated MAM formation is a potential target to overcome CP-resistance of OC."xsd:string |
| http://purl.uniprot.org/citations/35541901 | http://purl.org/dc/terms/identifier | "doi:10.7150/ijbs.71571"xsd:string |
| http://purl.uniprot.org/citations/35541901 | http://purl.uniprot.org/core/author | "Chen Z."xsd:string |
| http://purl.uniprot.org/citations/35541901 | http://purl.uniprot.org/core/author | "Chen Y."xsd:string |
| http://purl.uniprot.org/citations/35541901 | http://purl.uniprot.org/core/author | "Chen P."xsd:string |
| http://purl.uniprot.org/citations/35541901 | http://purl.uniprot.org/core/author | "Li J."xsd:string |
| http://purl.uniprot.org/citations/35541901 | http://purl.uniprot.org/core/author | "Zhang Q."xsd:string |
| http://purl.uniprot.org/citations/35541901 | http://purl.uniprot.org/core/author | "Zhang S."xsd:string |
| http://purl.uniprot.org/citations/35541901 | http://purl.uniprot.org/core/author | "Zhang C."xsd:string |
| http://purl.uniprot.org/citations/35541901 | http://purl.uniprot.org/core/author | "Yang Y."xsd:string |
| http://purl.uniprot.org/citations/35541901 | http://purl.uniprot.org/core/author | "Su H."xsd:string |
| http://purl.uniprot.org/citations/35541901 | http://purl.uniprot.org/core/author | "Su L."xsd:string |
| http://purl.uniprot.org/citations/35541901 | http://purl.uniprot.org/core/author | "Qi F."xsd:string |
| http://purl.uniprot.org/citations/35541901 | http://purl.uniprot.org/core/author | "Chen Y.'"xsd:string |
| http://purl.uniprot.org/citations/35541901 | http://purl.uniprot.org/core/date | "2022"xsd:gYear |
| http://purl.uniprot.org/citations/35541901 | http://purl.uniprot.org/core/name | "Int J Biol Sci"xsd:string |
| http://purl.uniprot.org/citations/35541901 | http://purl.uniprot.org/core/pages | "2914-2931"xsd:string |
| http://purl.uniprot.org/citations/35541901 | http://purl.uniprot.org/core/title | "GRP75-faciliated Mitochondria-associated ER Membrane (MAM) Integrity controls Cisplatin-resistance in Ovarian Cancer Patients."xsd:string |
| http://purl.uniprot.org/citations/35541901 | http://purl.uniprot.org/core/volume | "18"xsd:string |
| http://purl.uniprot.org/citations/35541901 | http://www.w3.org/2004/02/skos/core#exactMatch | http://purl.uniprot.org/pubmed/35541901 |
| http://purl.uniprot.org/citations/35541901 | http://xmlns.com/foaf/0.1/primaryTopicOf | https://pubmed.ncbi.nlm.nih.gov/35541901 |
| http://purl.uniprot.org/uniprot/#_A1XP52-mappedCitation-35541901 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/35541901 |
| http://purl.uniprot.org/uniprot/#_A0A384P5G6-mappedCitation-35541901 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/35541901 |
| http://purl.uniprot.org/uniprot/#_B7Z1V7-mappedCitation-35541901 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/35541901 |