N-glycosylation of GDF15 abolishes its inhibitory effect on EGFR in AR inhibitor-resistant prostate cancer cells

Wang, Rong; Wen, Piaopiao; Yang, Ganglong; Feng, Yanyan; Mi, Yuanyuan; Wang, Xiaoying; Zhu, S. Y.; Wang, Rong

doi:10.1038/s41419-022-05090-3

Cited by 11 publications

(4 citation statements)

References 45 publications

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“…Moreover, the signalling pathways related to the active ingredients in Fructus Ligustri Lucidi and Cuscutae Semen are closely related to AR. Downregulation of RAGE expression by RNAi inhibits cell proliferation in both androgendependent and androgen-independent PCa cells [47]. The 13 Computational and Mathematical Methods in Medicine PI3K-Akt signalling pathway is AR-dependent [48] and regulates Rb phosphorylation to enable AGE-RAGE interaction, which enhances PCa cell proliferation [49].…”

Section: Discussionmentioning

confidence: 99%

Assessing the Mechanism of Action of “Fructus Ligustri Lucidi-Cuscutae Semen” in Prostate Cancer Treatment Using Network Pharmacology and Molecular Docking

Shang

Guo

et al. 2022

Computational and Mathematical Methods in Medicine

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Objective. To explore the mechanism of action of “Fructus Ligustri Lucidi-Cuscutae Semen” in the treatment of prostate cancer using network pharmacology and molecular docking. Methods. The active ingredients and targets of “Fructus Ligustri Lucidi-Cuscutae Semen” were obtained by searching the TCMSP and DrugBank databases. These were matched and corrected using the UniProt platform. A drug “active ingredient-target” network map was constructed using Cytoscape 3.8.0. Prostate cancer-related targets were acquired from GeneCards, Disgenet, DrugBank, and other databases. The protein-protein interaction (PPI) network between the drug and prostate cancer was constructed with BioGenet; the crossover network of the two targets was extracted derive the key targets of “Fructus Ligustri Lucidi-Cuscutae Semen” for prostate cancer treatment. We used the Metascape platform for GO and KEGG enrichment analysis of the key targets. AutoDockTools1.5.6 and PyMOL software were used to perform molecular docking. Results. We obtained 13 active ingredients, 221 drug targets, 1511 prostate cancer targets (including 221 key targets), and 305 KEGG pathways from “Fructus Ligustri Lucidi-Cuscutae Semen.” Paclitaxel, quercetin, kaempferol, TP53, β-sitosterol, EGFR, and ESR1 in “Fructus Ligustri Lucidi-Cuscutae Semen” showed good docking activity. Conclusion. “Fructus Ligustri Lucidi-Cuscutae Semen” is a valuable clinical guide for the treatment of prostate cancer with multicomponent, multitarget, and multipathway characteristics.

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Section: Discussionmentioning

confidence: 99%

Assessing the Mechanism of Action of “Fructus Ligustri Lucidi-Cuscutae Semen” in Prostate Cancer Treatment Using Network Pharmacology and Molecular Docking

Shang

Guo

et al. 2022

Computational and Mathematical Methods in Medicine

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“…After an initial decrease in prostate weight, regaining prostate growth was considered the emergence of castration resistance. [ 26 ] The mice were randomly divided into ENZ (i.g. 10 mg Kg −1 ), POL (i.g.…”

Section: Methodsmentioning

confidence: 99%

Identification of PRDX5 as A Target for The Treatment of Castration‐Resistant Prostate Cancer

Wang,

Mi,

et al. 2023

Advanced Science

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Treatment of castration‐resistant prostate cancer (CRPC) is a long‐standing clinical challenge. Traditionally, CRPC drugs work by either reducing dihydrotestosterone biosynthesis or blocking androgen receptor (AR) signaling. Here it is demonstrated that AR inhibitor treatment gives rise to a drug‐tolerant persister (DTP) state. The thioredoxin/peroxiredoxin pathway is up‐regulated in DTP cells. Peroxiredoxin 5 (PRDX5) promotes AR inhibitor resistance and CRPC development. Inhibition of PRDX5 suppresses DTP cell proliferation in culture, dampens CRPC development in animal models, and stabilizes PSA progression and metastatic lesions in patients. Therefore, the study provides a novel mechanism and potential target for the management of castration‐resistant prostate cancer.

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“…KO and WT cells were cultured in DMEM (Biological Industries) containing 10% fetal bovine serum at 37 °C and 5% CO 2 . When the cells reached 80% confluence in a 100 mm dish, proteins were extracted as previously described [ 17 ]. In short, 6 × 10 6 cells were washed with 1 × phosphate-buffered saline (PBS) for 2 min, followed by 8 M urea and 1 M ammonium bicarbonate buffer on the dish and lysed for 30 min on ice.…”

Section: Methodsmentioning

confidence: 99%

Proteome and Glycoproteome Analyses Reveal the Protein N-Linked Glycosylation Specificity of STT3A and STT3B

Wen

Chen

Zuo

et al. 2022

Cells

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STT3A and STT3B are the main catalytic subunits of the oligosaccharyltransferase complex (OST-A and OST-B in mammalian cells), which primarily mediate cotranslational and post-translocational N-linked glycosylation, respectively. To determine the specificity of STT3A and STT3B, we performed proteomic and glycoproteomic analyses in the gene knock-out (KO) and wild-type HEK293 cells. In total, 3961 proteins, 4265 unique N-linked intact glycopeptides and 629 glycosites representing 349 glycoproteins were identified from all these cells. Deletion of the STT3A gene had a greater impact on the protein expression than deletion of STT3B, especially on glycoproteins. In addition, total mannosylated N-glycans were reduced and fucosylated N-glycans were increased in STT3A-KO cells, which were caused by the differential expression of glycan-related enzymes. Interestingly, hyperglycosylated proteins were identified in KO cells, and the hyperglycosylation of ENPL was caused by the endoplasmic reticulum (ER) stress due to the STT3A deletion. Furthermore, the increased expression of the ATF6 and PERK indicated that the unfolded protein response also happened in STT3A-KO cells. Overall, the specificity of STT3A and STT3B revealed that defects in the OST subunit not only broadly affect N-linked glycosylation of the protein but also affect protein expression.

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N-glycosylation of GDF15 abolishes its inhibitory effect on EGFR in AR inhibitor-resistant prostate cancer cells

Cited by 11 publications

References 45 publications

Assessing the Mechanism of Action of “Fructus Ligustri Lucidi-Cuscutae Semen” in Prostate Cancer Treatment Using Network Pharmacology and Molecular Docking

Assessing the Mechanism of Action of “Fructus Ligustri Lucidi-Cuscutae Semen” in Prostate Cancer Treatment Using Network Pharmacology and Molecular Docking

Identification of PRDX5 as A Target for The Treatment of Castration‐Resistant Prostate Cancer

Proteome and Glycoproteome Analyses Reveal the Protein N-Linked Glycosylation Specificity of STT3A and STT3B

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