FRINK Linked Data Fragments server

Matches in SemOpenAlex for { <https://semopenalex.org/work/W2395479113> ?p ?o ?g. }

• W2395479113 endingPage "PR01" @default.
• W2395479113 startingPage "PR01" @default.
• W2395479113 abstract "Abstract The objective of the present study is to identify modulators of cellular metabolism among transportome genes which could potentially be exploited as targets in pancreatic ductal adenocarcinoma (PDAC). Indeed cancer cells have the ability to adapt in order to survive stressful environment where oxygen and nutrients are limited due to the poor vasculature and outgrowth of stromal component. Thus, disrupting mechanisms of metabolic adaptation could inhibit tumor proliferation or sensitize tumor cells to treatment. Ion channels and transporters provide the link between cancer cells, stroma and matrix. Additionally these proteins may redirect metabolic fluxes among the cellular compartments which could provide alternative utilization of available substrates. We performed a Metabolic Flux Analyzer siRNA-based screen of transportome genes in Mia PaCa-2 cells to find transporters that influence either glycolysis (extracellular acidification rate) or oxidative phosphorylation (oxygen consumption rate). Among the hits SLC25A32 (Mitochondrial Folate Transporter) was identified to significantly increase oxygen consumption. SLC25A32 is poorly characterized in the literature and its function and role in tumorigenesis are currently unknown. The gene was shown to be expressed in the inner mitochondrial membrane and was identified as a bi-directional mitochondrial transporter of tetrahydroxyfolate (THF). Interestingly an inactivating mutation of SLC25A32 leads to glycine auxotrophy in CHO cells. Additionally, amplification of SLC25A32 is found in a large portion of cancers (breast, prostate, ovary and liver). This gene amplification confers poor prognosis in breast cancer patients. In depth follow-up studies revealed that siRNA-mediated inhibition of SLC25A32 caused an increase in mitochondrial reactive oxygen species (ROS) production, G2/M cell cycle arrest and subsequently cell death. MitoTEMPO, a mitochondrial targeted antioxidant, partially rescues this phenotype, indicating that ROS mediates the death phenotype upon SLC25A32 inhibition. Furthermore, mitochondrial gene expression profiling revealed that downregulation of SLC25A32 decreased the expression of anti-apoptotic genes (BCL2L, SFN), making cells more susceptible to death, and upregulated the mitochondrial uncoupler UCP-1, which explains the increase in oxygen consumption. In agreement with our knockdown studies, overexpression of SLC25A32 in Mia PaCa-2 cell line led to a decrease in oxygen consumption. Furthermore SLC25A32 overexpression augmented cell growth. Both these results confirm the role of SLC25A32 in modulating mitochondrial homeostasis and demonstrate that the amplification of this gene may provide advantage for cancer cell proliferation and survival. Based on our data, SLC25A32 might be a potential anti-cancer target for PDAC patients. Citation Format: Ilya Kovalenko, Laura Schöckel, Andrea Glasauer, Andrea Haegebarth, Sven Christian. Role of mitochondrial folate transporter in metabolism of tumor cells. [abstract]. In: Proceedings of the AACR Special Conference: Metabolism and Cancer; Jun 7-10, 2015; Bellevue, WA. Philadelphia (PA): AACR; Mol Cancer Res 2016;14(1_Suppl):Abstract nr PR01." @default.
• W2395479113 created "2016-06-24" @default.
• W2395479113 creator A5003724875 @default.
• W2395479113 creator A5020529398 @default.
• W2395479113 creator A5032600222 @default.
• W2395479113 creator A5056835247 @default.
• W2395479113 creator A5065261986 @default.
• W2395479113 date "2016-01-01" @default.
• W2395479113 modified "2023-09-24" @default.
• W2395479113 title "Abstract PR01: Role of mitochondrial folate transporter in metabolism of tumor cells" @default.
• W2395479113 doi "https://doi.org/10.1158/1557-3125.metca15-pr01" @default.
• W2395479113 hasPublicationYear "2016" @default.
• W2395479113 type Work @default.
• W2395479113 sameAs 2395479113 @default.
• W2395479113 citedByCount "1" @default.
• W2395479113 countsByYear W23954791132017 @default.
• W2395479113 crossrefType "journal-article" @default.
• W2395479113 hasAuthorship W2395479113A5003724875 @default.
• W2395479113 hasAuthorship W2395479113A5020529398 @default.
• W2395479113 hasAuthorship W2395479113A5032600222 @default.
• W2395479113 hasAuthorship W2395479113A5056835247 @default.
• W2395479113 hasAuthorship W2395479113A5065261986 @default.
• W2395479113 hasConcept C121608353 @default.
• W2395479113 hasConcept C16930146 @default.
• W2395479113 hasConcept C28859421 @default.
• W2395479113 hasConcept C502942594 @default.
• W2395479113 hasConcept C54355233 @default.
• W2395479113 hasConcept C555283112 @default.
• W2395479113 hasConcept C86803240 @default.
• W2395479113 hasConcept C95444343 @default.
• W2395479113 hasConcept C96232424 @default.
• W2395479113 hasConceptScore W2395479113C121608353 @default.
• W2395479113 hasConceptScore W2395479113C16930146 @default.
• W2395479113 hasConceptScore W2395479113C28859421 @default.
• W2395479113 hasConceptScore W2395479113C502942594 @default.
• W2395479113 hasConceptScore W2395479113C54355233 @default.
• W2395479113 hasConceptScore W2395479113C555283112 @default.
• W2395479113 hasConceptScore W2395479113C86803240 @default.
• W2395479113 hasConceptScore W2395479113C95444343 @default.
• W2395479113 hasConceptScore W2395479113C96232424 @default.
• W2395479113 hasIssue "1_Supplement" @default.
• W2395479113 hasLocation W23954791131 @default.
• W2395479113 hasOpenAccess W2395479113 @default.
• W2395479113 hasPrimaryLocation W23954791131 @default.
• W2395479113 hasRelatedWork W2029712941 @default.
• W2395479113 hasRelatedWork W2146971577 @default.
• W2395479113 hasRelatedWork W2152174105 @default.
• W2395479113 hasRelatedWork W2529729439 @default.
• W2395479113 hasRelatedWork W2619803380 @default.
• W2395479113 hasRelatedWork W2898479841 @default.
• W2395479113 hasRelatedWork W3031393368 @default.
• W2395479113 hasRelatedWork W3043922953 @default.
• W2395479113 hasRelatedWork W3173570487 @default.
• W2395479113 hasRelatedWork W3189559068 @default.
• W2395479113 hasVolume "14" @default.
• W2395479113 isParatext "false" @default.
• W2395479113 isRetracted "false" @default.
• W2395479113 magId "2395479113" @default.
• W2395479113 workType "article" @default.