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.
See: https://www.metabolomicsworkbench.org/about/howtocite.php
| Study ID | ST001989 |
| Study Title | THEM6-mediated lipid remodelling sustains stress resistance in cancer (Part 3) |
| Study Type | Lipidomics |
| Study 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 | IGMM |
| Last Name | Blanco |
| First Name | Giovanny |
| Address | Crewe Road South |
| g.blanco@ed.ac.uk | |
| Phone | +447526056849 |
| Submit Date | 2021-11-10 |
| Raw Data Available | Yes |
| Raw Data File Type(s) | mgf |
| Analysis Type Detail | LC-MS |
| Release Date | 2021-12-01 |
| Release Version | 1 |
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: | 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 |
|---|---|---|
| SA185972 | CWR_MYC_3_Set2_pos.raw | CWR22res_EV |
| SA185973 | CWR_MYC_3_Set3_pos.raw | CWR22res_EV |
| SA185974 | CWR_MYC_1_Set1_pos.raw | CWR22res_EV |
| SA185975 | CWR_MYC_2_Set3_pos.raw | CWR22res_EV |
| SA185976 | CWR_MYC_3_Set1_pos.raw | CWR22res_EV |
| SA185977 | CWR_MYC_1_Set2_pos.raw | CWR22res_EV |
| SA185978 | CWR_MYC_2_Set1_pos.raw | CWR22res_EV |
| SA185979 | CWR_MYC_1_Set3_pos.raw | CWR22res_EV |
| SA185980 | CWR_MYC_2_Set2_pos.raw | CWR22res_EV |
| SA185981 | CWR_T6_3_Set1_pos.raw | CWR22res_T6_OE |
| SA185982 | CWR_T6_3_Set2_pos.raw | CWR22res_T6_OE |
| SA185983 | CWR_T6_3_Set3_pos.raw | CWR22res_T6_OE |
| SA185984 | CWR_T6_2_Set3_pos.raw | CWR22res_T6_OE |
| SA185985 | CWR_T6_1_Set1_pos.raw | CWR22res_T6_OE |
| SA185986 | CWR_T6_1_Set2_pos.raw | CWR22res_T6_OE |
| SA185987 | CWR_T6_1_Set3_pos.raw | CWR22res_T6_OE |
| SA185988 | CWR_T6_2_Set1_pos.raw | CWR22res_T6_OE |
| SA185989 | CWR_T6_2_Set2_pos.raw | CWR22res_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 |
