Summary of Study ST001963

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 PR001250. The data can be accessed directly via it's Project DOI: 10.21228/M84M70 This work is supported by NIH grant, U2C- DK119886.

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Study IDST001963
Study TitleTHEM6-mediated lipid remodelling sustains stress resistance in cancer
Study TypeLipidomics
Study SummaryDespite the clinical benefit of androgen-deprivation therapy (ADT), the majority of patients with advanced prostate cancer (PCa) ultimately develop lethal castration-resistant prostate cancer (CRPC). In this study, we identified thioesterase superfamily member 6 (THEM6) as a marker of ADT resistance in PCa. In patients, THEM6 expression correlates with progressive disease and is associated with poor survival. THEM6 deletion reduces in vivo tumour growth and restores castration sensitivity in orthograft models of CRPC. Mechanistically, THEM6 is located at the endoplasmic reticulum (ER) membrane and controls lipid homeostasis by regulating intracellular levels of ether lipids. As a consequence, THEM6 loss in CRPC cells significantly alters ER function, preventing lipid-mediated induction of ATF4 and reducing de novo sterol biosynthesis. Finally, we show that THEM6 is required for the establishment of the MYC-induced stress response. Thus, similar to PCa, THEM6 loss significantly impairs tumorigenesis in the MYC-dependent subtype of triple negative breast cancer. Altogether our results highlight THEM6 as a novel component of the treatment-induced stress response and a promising target for the treatment of CRPC and MYC-driven cancer.
Institute
IGMM
Last NameBlanco
First NameGiovanny
AddressCrewe Road South
Emailg.blanco@ed.ac.uk
Phone+447526056849
Submit Date2021-11-03
Raw Data AvailableYes
Raw Data File Type(s)mgf
Analysis Type DetailLC-MS
Release Date2021-11-19
Release Version1
Giovanny Blanco Giovanny Blanco
https://dx.doi.org/10.21228/M84M70
ftp://www.metabolomicsworkbench.org/Studies/ application/zip

Select appropriate tab below to view additional metadata details:

Project:

Project ID:PR001250
Project DOI:doi: 10.21228/M84M70
Project Title:THEM6-mediated lipid remodelling sustains stress resistance in cancer
Project Type:Lipidomics
Project Summary:Despite the clinical benefit of androgen-deprivation therapy (ADT), the majority of patients with advanced prostate cancer (PCa) ultimately develop lethal castration-resistant prostate cancer (CRPC). In this study, we identified thioesterase superfamily member 6 (THEM6) as a marker of ADT resistance in PCa. In patients, THEM6 expression correlates with progressive disease and is associated with poor survival. THEM6 deletion reduces in vivo tumour growth and restores castration sensitivity in orthograft models of CRPC. Mechanistically, THEM6 is located at the endoplasmic reticulum (ER) membrane and controls lipid homeostasis by regulating intracellular levels of ether lipids. As a consequence, THEM6 loss in CRPC cells significantly alters ER function, preventing lipid-mediated induction of ATF4 and reducing de novo sterol biosynthesis. Finally, we show that THEM6 is required for the establishment of the MYC-induced stress response. Thus, similar to PCa, THEM6 loss significantly impairs tumorigenesis in the MYC-dependent subtype of triple negative breast cancer. Altogether our results highlight THEM6 as a novel component of the treatment-induced stress response and a promising target for the treatment of CRPC and MYC-driven cancer.
Institute:Beatson Institute for Cancer Research
Last Name:Rodriguez Blanco
First Name:Giovanny
Address:Crewe Road South, Edinburgh, Midlothian, EH42XU, United Kingdom
Email:g.blanco@ed.ac.uk
Phone:00447526056849

Subject:

Subject ID:SU002043
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 Condition
SA184808T0_1_Al_exp1T0_1_Al
SA184809T0_1_Al_exp3T0_1_Al
SA184810T0_1_Al_exp2T0_1_Al
SA184811T0_2_Al_exp3T0_2_Al
SA184812T0_2_Al_exp1T0_2_Al
SA184813T0_2_Al_exp2T0_2_Al
SA184814T0_3_Al_exp3T0_3_Al
SA184815T0_3_Al_exp1T0_3_Al
SA184816T0_3_Al_exp2T0_3_Al
SA184817T1_1_Al_exp1T1_1_Al
SA184818T1_1_Al_exp3T1_1_Al
SA184819T1_1_Al_exp2T1_1_Al
SA184820T1_2_Al_exp3T1_2_Al
SA184821T1_2_Al_exp2T1_2_Al
SA184822T1_2_Al_exp1T1_2_Al
SA184823T1_3_Al_exp1T1_3_Al
SA184824T1_3_Al_exp3T1_3_Al
SA184825T1_3_Al_exp2T1_3_Al
SA184826T7_1_Al_exp3T7_1_Al
SA184827T7_1_Al_exp1T7_1_Al
SA184828T7_1_Al_exp2T7_1_Al
SA184829T7_2_Al_exp3T7_2_Al
SA184830T7_2_Al_exp1T7_2_Al
SA184831T7_2_Al_exp2T7_2_Al
SA184832T7_3_Al_exp3T7_3_Al
SA184833T7_3_Al_exp2T7_3_Al
SA184834T7_3_Al_exp1T7_3_Al
Showing results 1 to 27 of 27

Collection:

Collection ID:CO002036
Collection Summary:Lipids were extracted monophasic extractions of a mixture 1:1 of butanol-methanol (BuMe)
Sample Type:LnCap cells

Treatment:

Treatment ID:TR002055
Treatment Summary:These cells are CRISPR KOs of THEM6.

Sample Preparation:

Sampleprep ID:SP002049
Sampleprep Summary:Monophasic extraction straight from cell plates using BuMe or IPA.

Combined analysis:

Analysis ID AN003200 AN003201
Analysis type MS MS
Chromatography type Reversed phase Reversed phase
Chromatography system Thermo Dionex Ultimate 3000 Thermo Dionex Ultimate 3000
Column Waters Acquity CSH C18 (100 x 2.1mm,1.7um) Waters Acquity CSH C18 (100 x 2.1mm,1.7um)
MS Type ESI ESI
MS instrument type Orbitrap Orbitrap
MS instrument name Thermo Q Exactive Orbitrap Thermo Q Exactive Orbitrap
Ion Mode POSITIVE NEGATIVE
Units Peak Area Peak area

Chromatography:

Chromatography ID:CH002366
Chromatography Summary:Please see methods
Instrument Name:Thermo Dionex Ultimate 3000
Column Name:Waters Acquity CSH C18 (100 x 2.1mm,1.7um)
Chromatography Type:Reversed phase

MS:

MS ID:MS002978
Analysis ID:AN003200
Instrument Name:Thermo Q Exactive Orbitrap
Instrument Type:Orbitrap
MS Type:ESI
MS Comments:See Methods file.
Ion Mode:POSITIVE
  
MS ID:MS002979
Analysis ID:AN003201
Instrument Name:Thermo Q Exactive Orbitrap
Instrument Type:Orbitrap
MS Type:ESI
MS Comments:See Methods file.
Ion Mode:NEGATIVE
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