Summary of Study ST001989

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 IDST001989
Study TitleTHEM6-mediated lipid remodelling sustains stress resistance in cancer (Part 3)
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 Date2021-11-10
Raw Data AvailableYes
Raw Data File Type(s)mgf
Analysis Type DetailLC-MS
Release Date2021-12-01
Release Version1
Giovanny Blanco Giovanny Blanco
https://dx.doi.org/10.21228/M84M70
ftp://www.metabolomicsworkbench.org/Studies/ application/zip

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Combined analysis:

Analysis ID AN003241
Analysis type MS
Chromatography type Reversed phase
Chromatography system Thermo Dionex Ultimate 3000
Column Waters Acquity CSH C18 (100 x 2.1mm,1.7um)
MS Type ESI
MS instrument type Orbitrap
MS instrument name Thermo Q Exactive Orbitrap
Ion Mode POSITIVE
Units Peak Area

MS:

MS ID:MS003014
Analysis ID:AN003241
Instrument Name:Thermo Q Exactive Orbitrap
Instrument Type:Orbitrap
MS Type:ESI
MS Comments:See Methods file.
Ion Mode:POSITIVE
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