DECR1 is an androgen-repressed survival factor that regulates PUFA oxidation to protect prostate tumor cells from ferroptosis

Nassar, Zeyad D.; Mah, Chui Yan; Dehairs, Jonas; Burvenich, Ingrid; Irani, Swati; Centenera, Margaret M.; Shrestha, Raj K.; Moldovan, Max; Don, Anthony S.; Scott, Andrew M.; Horvath, Lisa G.; Lynn, David J.; Selth, Luke A.; Hoy, Andrew J.; Swinnen, Johannes V.; Butler, Lisa M.

doi:10.1101/865626

Cited by 4 publications

(4 citation statements)

References 86 publications

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“…DECR1 can cause PUFA depletion in prostate cancer by encoding the rate-limiting enzyme of PUFA oxidation, thus protecting prostate cancer from ferroptosis. Targeting to DECR1 can cause PUFA to accumulate in cells, enhanced oxidative stress and lipids peroxidation, and finally induce ferroptosis (Nassar et al, 2020;Yang et al, 2021). Erastin and RSL3, showing a good ability to induce ferroptosis in prostate cancer in vitro and suppress this malignancy (Yang et al, 2021;Ghoochani A et al, 2021).…”

Section: Rcds In Prostate Malignanciesmentioning

confidence: 99%

Regulated Cell Death in Urinary Malignancies

Nie

Chen

Gao

et al. 2021

Front. Cell Dev. Biol.

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Urinary malignancies refer to a series of malignant tumors that occur in the urinary system and mainly include kidney, bladder, and prostate cancers. Although local or systemic radiotherapy and chemotherapy, immunotherapy, castration therapy and other methods have been applied to treat these diseases, their high recurrence and metastasis rate remain problems for patients. With in-depth research on the pathogenesis of urinary malignant tumors, this work suggests that regulatory cell death (RCD) plays an important role in their occurrence and development. These RCD pathways are stimulated by various internal and external environmental factors and can induce cell death or permit cell survival under the control of various signal molecules, thereby affecting tumor progression or therapeutic efficacy. Among the previously reported RCD methods, necroptosis, pyroptosis, ferroptosis, and neutrophil extracellular traps (NETs) have attracted research attention. These modes transmit death signals through signal molecules, such as cysteine-aspartic proteases (caspase) family and tumor necrosis factor-α (TNF-α) that have a wide and profound influence on tumor proliferation or death and even change the sensitivity of tumor cells to therapy. This review discussed the effects of necroptosis, pyroptosis, ferroptosis, and NETs on kidney, bladder and prostate cancer and summarized the latest research and achievements in these fields. Future directions and possibility of improving the denouement of urinary system tumors treatment by targeting RCD therapy were also explored.

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Section: Rcds In Prostate Malignanciesmentioning

confidence: 99%

Regulated Cell Death in Urinary Malignancies

Nie

Chen

Gao

et al. 2021

Front. Cell Dev. Biol.

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“…DcytB, duodenal cytochrome b; DMT1, divalent metal transporter 1; FPN, ferroportin; HP, hephaestin; TF, transferrin; TFR1, transferrin receptor 1; TFR2, transferrin receptor 2; STEAP3, six-transmembrane epithelial antigen of prostate 3; ROS, reactive oxygen species; ATG, autophagy associated gene; NCOA4, nuclear receptor coactivator 4; IRPs, iron response element binding proteins; PCBP, poly(rC)-binding proteins; HSP, heat shock protein; NRF2, nuclear factor erythroid 2-related factor 2. (48,49). This indicates that fatty acid b-oxidation plays a crucial function in balancing PUFAs and MUFAs.…”

Section: Lipid Peroxidationmentioning

confidence: 98%

Mechanisms and regulations of ferroptosis

Zhang,

Liu,

Wang

et al. 2023

Front. Immunol.

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Regulation of cell mortality for disease treatment has been the focus of research. Ferroptosis is an iron-dependent regulated cell death whose mechanism has been extensively studied since its discovery. A large number of studies have shown that regulation of ferroptosis brings new strategies for the treatment of various benign and malignant diseases. Iron excess and lipid peroxidation are its primary metabolic features. Therefore, genes involved in iron metabolism and lipid metabolism can regulate iron overload and lipid peroxidation through direct or indirect pathways, thereby regulating ferroptosis. In addition, glutathione (GSH) is the body’s primary non-enzymatic antioxidants and plays a pivotal role in the struggle against lipid peroxidation. GSH functions as an auxiliary substance for glutathione peroxidase 4 (GPX4) to convert toxic lipid peroxides to their corresponding alcohols. Here, we reviewed the researches on the mechanism of ferroptosis in recent years, and comprehensively analyzed the mechanism and regulatory process of ferroptosis from iron metabolism and lipid metabolism, and then described in detail the metabolism of GPX4 and the main non-enzymatic antioxidant GSH in vivo.

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“…Expression of the elongated very-long-chain fatty acid protein 5 and fatty acid desaturase has been found to enhance the synthesis of more elongated and desaturated PUFA species that promote ferroptosis sensitivity [63][64] . As a rate-limiting enzyme in the β-oxidation process, 2,4-dienoyl-CoA reductase 1 is involved in the catabolism of PUFAs in mitochondria, and the loss of 2,4-dienoyl-CoA reductase 1 function may lead to the accumulation of intracellular PUFAs and increase ferroptosis sensitivity [65] .…”

Section: Acsl4-lpcat3-aa/ada-pes Axismentioning

confidence: 99%

Ferroptosis: Iron-mediated cell death linked to disease pathogenesis

Zhang,

Hu,

Wang

et al. 2024

J Biomed Res

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Ferroptosis is an iron-mediated regulatory cell death pattern characterized by oxidative damage. The molecular regulating mechanisms are related to iron metabolism, lipid peroxidation, and glutathione metabolism. Additionally, some immunological signaling pathways, such as the cGAS-STING axis, JAK-STAT1 axis, and TGF-β1-Smad3 axis may also participate in the regulation of ferroptosis. Studies have shown that ferroptosis is closely related to many diseases such as cancer, neurodegenerative diseases, inflammatory diseases, and autoimmune diseases. Considering the pivotal role of ferroptosis-regulating signaling in the pathogenesis of diverse diseases, the development of ferroptosis inducers or inhibitors may have significant clinical potential for the treatment of the aforementioned conditions.

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DECR1 is an androgen-repressed survival factor that regulates PUFA oxidation to protect prostate tumor cells from ferroptosis

Cited by 4 publications

References 86 publications

Regulated Cell Death in Urinary Malignancies

Regulated Cell Death in Urinary Malignancies

Mechanisms and regulations of ferroptosis

Ferroptosis: Iron-mediated cell death linked to disease pathogenesis

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