Summary of Study ST002054

This data is available at the NIH Common Fund's National Metabolomics Data Repository (NMDR) website, the Metabolomics Workbench, https://www.metabolomicsworkbench.org, where it has been assigned Project ID PR001299. The data can be accessed directly via it's Project DOI: 10.21228/M8T13T This work is supported by NIH grant, U2C- DK119886.

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This study contains a large results data set and is not available in the mwTab file. It is only available for download via FTP as data file(s) here.

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Study IDST002054
Study TitleReduced ER-mitochondria connectivity promotes neuroblastoma multidrug resistance
Study SummaryMost cancer deaths result from progression of therapy resistant disease, yet our understanding of this phenotype is limited. Cancer therapies generate stress signals that act upon mitochondria to initiate apoptosis. Mitochondria isolated from neuroblastoma cells were exposed to tBid or Bim, death effectors activated by therapeutic stress. Multidrug resistant tumor cells obtained from children at relapse had markedly attenuated Bak and Bax oligomerization and cytochrome c release (surrogates for apoptotic commitment) in comparison with patient-matched tumor cells obtained at diagnosis. Electron microscopy identified reduced endoplasmic reticulum-mitochondria contacts (ERMCs) in therapy resistant cells, and genetically or biochemically reducing ERMCs in therapy sensitive tumors phenocopied resistance. ERMCs serve as platforms to transfer Ca2+ and bioactive lipids to mitochondria. Reduced Ca2+ transfer was found in some but not all resistant cells, and inhibiting transfer did not attenuate apoptotic signaling. In contrast, reduced ceramide synthesis and transfer was common to resistant cells and its inhibition induced stress resistance. We identify ERMCs as physiologic regulators of apoptosis via ceramide transfer and uncover a previously unrecognized mechanism for cancer multidrug resistance.
Institute
Columbia University
DepartmentNeurology
LaboratoryArea-Gomez Lab
Last NameYun
First NameTaekyung
Address650 W 168th Street
Emailtdy2102@cumc.columbia.edu
Phone212-305-3836
Submit Date2021-11-18
Raw Data AvailableYes
Raw Data File Type(s)raw(Waters)
Analysis Type DetailLC-MS
Release Date2022-01-17
Release Version1
Taekyung Yun Taekyung Yun
https://dx.doi.org/10.21228/M8T13T
ftp://www.metabolomicsworkbench.org/Studies/ application/zip

Select appropriate tab below to view additional metadata details:

Project:

Project ID:PR001299
Project DOI:doi: 10.21228/M8T13T
Project Title:Reduced ER-mitochondria connectivity promotes neuroblastoma multidrug resistance
Project Summary:Most cancer deaths result from progression of therapy resistant disease, yet our understanding of this phenotype is limited. Cancer therapies generate stress signals that act upon mitochondria to initiate apoptosis. Mitochondria isolated from neuroblastoma cells were exposed to tBid or Bim, death effectors activated by therapeutic stress. Multidrug resistant tumor cells obtained from children at relapse had markedly attenuated Bak and Bax oligomerization and cytochrome c release (surrogates for apoptotic commitment) in comparison with patient-matched tumor cells obtained at diagnosis. Electron microscopy identified reduced endoplasmic reticulum-mitochondria contacts (ERMCs) in therapy resistant cells, and genetically or biochemically reducing ERMCs in therapy sensitive tumors phenocopied resistance. ERMCs serve as platforms to transfer Ca2+ and bioactive lipids to mitochondria. Reduced Ca2+ transfer was found in some but not all resistant cells, and inhibiting transfer did not attenuate apoptotic signaling. In contrast, reduced ceramide synthesis and transfer was common to resistant cells and its inhibition induced stress resistance. We identify ERMCs as physiologic regulators of apoptosis via ceramide transfer and uncover a previously unrecognized mechanism for cancer multidrug resistance.
Institute:Columbia University - Medical Center
Department:Neurology
Laboratory:Area-Gomez Lab
Last Name:Yun
First Name:Taekyung
Address:650 W 168th Street, New York, NY, 10032, USA
Email:tdy2102@cumc.columbia.edu
Phone:212-305-3836

Subject:

Subject ID:SU002136
Subject Type:Cultured cells
Subject Species:Homo sapiens
Taxonomy ID:9606

Factors:

Subject type: Cultured cells; Subject species: Homo sapiens (Factor headings shown in green)

mb_sample_id local_sample_id Genotype
SA1936982021_06_16_Jorida_Run 16BE 1
SA1936992021_06_16_Jorida_Run 26BE 1
SA1937002021_06_16_Jorida_Run 27BE 1
SA1937012021_06_16_Jorida_Run 04BE 2
SA1937022021_06_16_Jorida_Run 07BE 2
SA1937032021_06_16_Jorida_Run 32BE 2
SA1937042021_06_16_Jorida_Run 19CHLA 122
SA1937052021_06_16_Jorida_Run 29CHLA 122
SA1937062021_06_16_Jorida_Run 12CHLA 122
SA1937072021_06_16_Jorida_Run 05CHLA 122
SA1937082021_06_16_Jorida_Run 31CHLA 136
SA1937092021_06_16_Jorida_Run 08CHLA 136
SA1937102021_06_16_Jorida_Run 02CHLA 136
SA1937112021_06_16_Jorida_Run 15CHLA 136
SA1937122021_06_16_Jorida_Run 22CHLA 15
SA1937132021_06_16_Jorida_Run 10CHLA 15
SA1937142021_06_16_Jorida_Run 20CHLA 15
SA1937152021_06_16_Jorida_Run 06CHLA 15
SA1937162021_06_16_Jorida_Run 18CHLA 20
SA1937172021_06_16_Jorida_Run 11CHLA 20
SA1937182021_06_16_Jorida_Run 21CHLA 20
SA1937192021_06_16_Jorida_Run 30COGN 144
SA1937202021_06_16_Jorida_Run 03COGN 144
SA1937212021_06_16_Jorida_Run 28COGN 144
SA1937222021_06_16_Jorida_Run 13COGN 144
SA1937232021_06_16_Jorida_Run 14COGN 145
SA1937242021_06_16_Jorida_Run 23COGN 145
SA1937252021_06_16_Jorida_Run 24COGN 145
Showing results 1 to 28 of 28

Collection:

Collection ID:CO002129
Collection Summary:Cells were collected in cold PBS and suspended in cold Buffer A with protease inhibitor at 10 million cells/ml
Sample Type:Cultured cells

Treatment:

Treatment ID:TR002148
Treatment Summary:Cells were treated with IMDM Media 12440 supplemented in 10% fetal bovine serum, 2mM L-glutamine, 1% ITS, 100U/ml of penicillin and 100 mcg/ml gentamycin. Cell cultures were incubated at 37 degree Celsius in a humidified atmosphere of 5% CO2.

Sample Preparation:

Sampleprep ID:SP002142
Sampleprep Summary:Lipids were extracted from the cell pellet (Bligh/Dyer). 900 ul chlorofrom/methanol (1/2) into the cell pellet, then incubated at 4C for 1 hour agigated (300rpm). Chloroform(300ul) and MQ water(250ul) were added discrete order, then vortex and cetrifuged for 2min at 9000 rpm. Bottom organic phase was collected and dried using vacuum concentrator.

Combined analysis:

Analysis ID AN003344 AN003345
Analysis type MS MS
Chromatography type Reversed phase Reversed phase
Chromatography system Waters Acquity I-Class Waters Acquity I-Class
Column Waters Acquity BEH HSS T3 (150x 2.1mm,1.8um) Waters Acquity BEH HSS T3 (150x 2.1mm,1.8um)
MS Type ESI ESI
MS instrument type QTOF QTOF
MS instrument name Waters Synapt G2 Si QTOF Waters Synapt G2 Si QTOF
Ion Mode POSITIVE NEGATIVE
Units uM uM

Chromatography:

Chromatography ID:CH002476
Instrument Name:Waters Acquity I-Class
Column Name:Waters Acquity BEH HSS T3 (150x 2.1mm,1.8um)
Chromatography Type:Reversed phase

MS:

MS ID:MS003113
Analysis ID:AN003344
Instrument Name:Waters Synapt G2 Si QTOF
Instrument Type:QTOF
MS Type:ESI
MS Comments:Raw data were converted into ABF files using Analysis Base File Converter. These converted files were used for MS-Dial to align/identify peaks/calculate peak area.
Ion Mode:POSITIVE
  
MS ID:MS003114
Analysis ID:AN003345
Instrument Name:Waters Synapt G2 Si QTOF
Instrument Type:QTOF
MS Type:ESI
MS Comments:Raw data were converted into ABF files using Analysis Base File Converter. These converted files were used for MS-Dial to align/identify peaks/calculate peak area.
Ion Mode:NEGATIVE
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