Summary of Study ST001988

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 IDST001988
Study TitleTHEM6-mediated lipid remodelling sustains stress resistance in cancer (Part 2)
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:SU002069
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
SA185945T2_3_22_exp2_pos.raw22rv1_CTL
SA185946T2_3_22_exp3_pos.raw22rv1_CTL
SA185947T2_2_22_exp3_pos.raw22rv1_CTL
SA185948T2_1_22_exp1_pos.raw22rv1_CTL
SA185949T2_3_22_exp1_pos.raw22rv1_CTL
SA185950T2_1_22_exp2_pos.raw22rv1_CTL
SA185951T2_2_22_exp1_pos.raw22rv1_CTL
SA185952T2_1_22_exp3_pos.raw22rv1_CTL
SA185953T2_2_22_exp2_pos.raw22rv1_CTL
SA185954T4_3_22_pos_181213160812.raw22rv1_T6_KO1
SA185955T4_3_22_exp2_pos.raw22rv1_T6_KO1
SA185956T4_3_22_exp3_pos.raw22rv1_T6_KO1
SA185957T4_2_22_exp3_pos.raw22rv1_T6_KO1
SA185958T4_2_22_exp2_pos.raw22rv1_T6_KO1
SA185959T4_2_22_exp1_pos.raw22rv1_T6_KO1
SA185960T4_1_22_exp2_pos.raw22rv1_T6_KO1
SA185961T4_1_22_exp1_pos.raw22rv1_T6_KO1
SA185962T4_1_22_exp3_pos.raw22rv1_T6_KO1
SA185963T8_3_22_exp1_pos.raw22rv1_T6_KO2
SA185964T8_3_22_exp2_pos.raw22rv1_T6_KO2
SA185965T8_3_22_exp3_pos.raw22rv1_T6_KO2
SA185966T8_2_22_exp3_pos.raw22rv1_T6_KO2
SA185967T8_2_22_exp1_pos.raw22rv1_T6_KO2
SA185968T8_1_22_exp1_pos.raw22rv1_T6_KO2
SA185969T8_1_22_exp2_pos.raw22rv1_T6_KO2
SA185970T8_1_22_exp3_pos.raw22rv1_T6_KO2
SA185971T8_2_22_exp2_pos.raw22rv1_T6_KO2
Showing results 1 to 27 of 27

Collection:

Collection ID:CO002062
Collection Summary:Lipids were extracted monophasic extractions of a mixture 1:1 of butanol-methanol (BuMe)
Sample Type:LnCap cells

Treatment:

Treatment ID:TR002081
Treatment Summary:These cells are CRISPR KOs of THEM6.

Sample Preparation:

Sampleprep ID:SP002075
Sampleprep Summary:Monophasic extraction straight from cell plates using BuMe or IPA.

Combined analysis:

Analysis ID AN003240
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:CH002389
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:MS003013
Analysis ID:AN003240
Instrument Name:Thermo Q Exactive Orbitrap
Instrument Type:Orbitrap
MS Type:ESI
MS Comments:See Methods file.
Ion Mode:POSITIVE
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