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 2 publications

(2 citation statements)

References 86 publications

(50 reference statements)

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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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“…The role of ferroptosis in PCa has drawn attention in recent years. Butler et al's study revealed that knockdown of DECR1 in PCa cells inhibits tumor cells proliferation and migration via accumulating cellular polyunsaturated fatty acids (PUFAs), enhancing mitochondrial oxidative stress and lipid peroxidation, and promoting ferroptosis [13].…”

Section: Introductionmentioning

confidence: 99%

Identification and validation of a ferroptosis-related genes based prognostic signature for prostate cancer

Liu

Gao

et al. 2020

Preprint

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Ferroptosis, an iron-dependent form of selective cell death, involves in the development of many cancers. However, systematic analysis of ferroptosis related genes (FRGs) in prostate cancer (PCa) remains to be clarified. In our research, we collected the mRNA expression profiles and clinical information of PCa patients from TCGA and MSKCC databases. The univariate, LASSO and multivariate Cox regression method were performed to construct prognostic signature in TCGA cohort. Seven FRGs, AKR1C3, ALOXE3, ATP5MC3, CARS1, MT1G, PTGS2, TFRC, were included to establish the risk model, which was validated in MSKCC dataset. Subsequently, we found that high risk group was strongly correlated with copy number alteration load, tumor burden mutation, immune cell infiltration, mRNAsi, immuetherapy and bicalutamide response. Finally, it was identified that overexpression of TFRC could induce proliferation and invasion in PCa cell lines in vitro. These results demonstrated that this risk model based on recurrence free survival (RFS) could accurately predict prognosis in PCa patients, suggesting that FRGs are promising prognostic biomarkers and drug target genes for PCa patients.

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

Cited by 2 publications

References 86 publications

Regulated Cell Death in Urinary Malignancies

Regulated Cell Death in Urinary Malignancies

Identification and validation of a ferroptosis-related genes based prognostic signature for prostate cancer

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