ArticleEMBO molecular medicine2022
THEM6-mediated reprogramming of lipid metabolism supports treatment resistance in prostate cancer.
Article in EMBO molecular medicine, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers.
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Who cites it
22 citing papers in PubMed, 37 citations in OpenAlex.
- Comparative Analysis of Alcohol and Aldehyde Dehydrogenase Activities in Prostate Cancer and Benign Prostatic Hyperplasia.Journal of clinical medicine · 2026Article
- GSTM4 Suppresses Prostate Cancer Progression by Targeting TRIM27-mediated ACLY Ubiquitination and Lipid Metabolism.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- ZDHHC2-Dependent Palmitoylation Dictates Ferroptosis and Castration Sensitivity in Prostate Cancer via Controlling ACSL4 Degradation and Lipid Peroxidation.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- From biosynthesis to function: the roles of ether lipids in cancer development and treatment.Lipids in health and disease · 2025Review
- WTAP-mediated mScience China. Life sciences · 2025Article
- Alzheimer's disease-associated PLCG2 variants alter microglial state and function in human induced pluripotent stem cell-derived microglia-like cells.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2025Article
- THEM6 modulates carboplatin sensitivity by regulating ferroptosis through FDFT1 in triple-negative breast cancer.Breast cancer research : BCR · 2025Article
- Periprostatic Adipose Tissue as a Contributor to Prostate Cancer Pathogenesis: A Narrative Review.Cancers · 2025Review
- Adipose Tissues Have Been Overlooked as Players in Prostate Cancer Progression.International journal of molecular sciences · 2024Review
- The Altered Lipid Composition and Key Lipid Metabolic Enzymes in Thiacloprid-ResistantInternational journal of molecular sciences · 2024Article
- Identification of immune-related prognostic biomarkers in triple-negative breast cancer.Translational cancer research · 2024Article
- Activating transcription factor 4: a regulator of stress response in human cancers.Frontiers in cell and developmental biology · 2024Review
- Metabolic Adaptation and Cellular Stress Response As Targets for Cancer Therapy.The world journal of men's health · 2024Review
- THEM6 is a prognostic biomarker for breast cancer and is associated with immune infiltration.Scientific reports · 2023Article
- Emerging proteins involved in castration‑resistant prostate cancer via the AR‑dependent and AR‑independent pathways (Review).International journal of oncology · 2023Review
- SEC23A confers ER stress resistance in gastric cancer by forming the ER stress-SEC23A-autophagy negative feedback loop.Journal of experimental & clinical cancer research : CR · 2023Article
- Systematic analyses of GWAS summary statistics from UK Biobank identified novel susceptibility loci and genes for upper gastrointestinal diseases.Journal of human genetics · 2023Article
- Cell cycle protein BORA is associated with colorectal cancer progression by AURORA-PLK1 cascades: a bioinformatics analysis.Journal of cell communication and signaling · 2023Article
- Can THEM6 targeting stop resistance to prostate cancer treatment?EMBO molecular medicine · 2022Article
- THEM6-mediated reprogramming of lipid metabolism supports treatment resistance in prostate cancer.EMBO molecular medicine · 2022Article
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Authors and funding
37 authors at 6 institutions in 3 countries.
Funding
Abstract
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. THEM6 deletion reduces in vivo tumour growth and restores castration sensitivity in orthograft models of CRPC. Mechanistically, we show that the ER membrane-associated protein THEM6 regulates intracellular levels of ether lipids and is essential to trigger the induction of the ER stress response (UPR). Consequently, THEM6 loss in CRPC cells significantly alters ER function, reducing de novo sterol biosynthesis and preventing lipid-mediated activation of ATF4. Finally, we demonstrate that high THEM6 expression is associated with poor survival and correlates with high levels of UPR activation in PCa patients. Altogether, our results highlight THEM6 as a novel driver of therapy resistance in PCa as well as a promising target for the treatment of CRPC.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.