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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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:SU002070
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
SA185972CWR_MYC_3_Set2_pos.rawCWR22res_EV
SA185973CWR_MYC_3_Set3_pos.rawCWR22res_EV
SA185974CWR_MYC_1_Set1_pos.rawCWR22res_EV
SA185975CWR_MYC_2_Set3_pos.rawCWR22res_EV
SA185976CWR_MYC_3_Set1_pos.rawCWR22res_EV
SA185977CWR_MYC_1_Set2_pos.rawCWR22res_EV
SA185978CWR_MYC_2_Set1_pos.rawCWR22res_EV
SA185979CWR_MYC_1_Set3_pos.rawCWR22res_EV
SA185980CWR_MYC_2_Set2_pos.rawCWR22res_EV
SA185981CWR_T6_3_Set1_pos.rawCWR22res_T6_OE
SA185982CWR_T6_3_Set2_pos.rawCWR22res_T6_OE
SA185983CWR_T6_3_Set3_pos.rawCWR22res_T6_OE
SA185984CWR_T6_2_Set3_pos.rawCWR22res_T6_OE
SA185985CWR_T6_1_Set1_pos.rawCWR22res_T6_OE
SA185986CWR_T6_1_Set2_pos.rawCWR22res_T6_OE
SA185987CWR_T6_1_Set3_pos.rawCWR22res_T6_OE
SA185988CWR_T6_2_Set1_pos.rawCWR22res_T6_OE
SA185989CWR_T6_2_Set2_pos.rawCWR22res_T6_OE
Showing results 1 to 18 of 18

Collection:

Collection ID:CO002063
Collection Summary:Lipids were extracted monophasic extractions of a mixture 1:1 of butanol-methanol (BuMe)
Sample Type:LnCap cells

Treatment:

Treatment ID:TR002082
Treatment Summary:These cells are CRISPR KOs of THEM6.

Sample Preparation:

Sampleprep ID:SP002076
Sampleprep Summary:Monophasic extraction straight from cell plates using BuMe or IPA.

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

Chromatography:

Chromatography ID:CH002390
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: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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