Disturbing <scp>NLRP3</scp> acetylation and inflammasome assembly inhibits androgen receptor‐promoted inflammatory responses and prostate cancer progression

Zhao, An‐Ning; Yang, Zhan; Wang, Dandan; Shi, Bei; Zhang, Hong; Bai, Yang; Yan, Bo‐Wen; Zhang, Yong; Wen, Jin‐Kun; Wang, Xiaolu; Qu, Chun-Ying

doi:10.1096/fj.202200673rrr

Cited by 14 publications

(9 citation statements)

References 67 publications

(136 reference statements)

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“…These cells were incubated at RPMI 1640 or DMEM supplemented with 10% FBS and 1% penicillin/streptomycin. These cells tested negative for mycoplasma and incubated in humidified environments containing 95% air and 5% carbon dioxide (CO 2 ), as previously described 22,23 . Docetaxel (Doce) and elesclomol (ES) and tetrathiomolybdate (TTM), and rapamycin (Rapa) were dissolved in DMSO, while CuCl 2 in water.…”

Section: Methodsmentioning

confidence: 99%

Cuproptosis enhances docetaxel chemosensitivity by inhibiting autophagy via the DLAT/mTOR pathway in prostate cancer

Wen

Zhu

et al. 2023

The FASEB Journal

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Cuproptosis, a newly discovered programmed cell death induced by copper ions, is associated with the progression and drug resistance of various tumors. Docetaxel plays a vital role as a first‐line chemotherapeutic agent for advanced prostate cancer; however, most patients end up with prostate cancer progression because of inherent or acquired resistance. Herein, we examined the role of cuproptosis in the chemotherapeutic resistance of prostate cancer to docetaxel. We treated prostate cancer cell lines with elesclomol–CuCl2, as well as with docetaxel. We performed analyses of CCK8, colony formation tests, cell cycle flow assay, transmission electron microscopy, and mTOR signaling in treated cells, and treated a xenograft prostate cancer model with elesclomol–CuCl2 and docetaxel in vivo, and performed immunohistochemistry and Western blotting analysis in treated tumors. We found that elesclomol–CuCl2 could promote cell death and enhance chemosensitivity to docetaxel. Elesclomol–CuCl2 induced cell death and inhibited the growth of prostate cancer cells relying on copper ions‐induced cuproptosis, not elesclomol. In addition, dihydrolipoamide S‐acetyltransferase (DLAT) was involved in cuproptosis‐enhanced drug sensitivity to docetaxel. Mechanistically, upregulated DLAT by cuproptosis inhibited autophagy, promoted G2/M phase retention of cells, and enhanced the sensitivity to docetaxel chemotherapy in vitro and in vivo via the mTOR signaling pathway. Our findings demonstrated that the cuproptosis‐regulated DLAT/mTOR pathway inhibited autophagy and promoted cells in G2/M phase retention, thus enhancing the chemosensitivity to docetaxel. This discovery may provide an effective therapeutic option for treating advanced prostate cancer by inhibiting the chemotherapeutic resistance to docetaxel.

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Section: Methodsmentioning

confidence: 99%

Cuproptosis enhances docetaxel chemosensitivity by inhibiting autophagy via the DLAT/mTOR pathway in prostate cancer

Wen

Zhu

et al. 2023

The FASEB Journal

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“…In prostate cancer, circAR-3—a circular RNA (circRNA) derived from the androgen receptor gene—mediates NLRP3 acetylation by KAT2B, promoting inflammasome assembly and advancing tumor progression. 479 Both lncRNAs and miRNAs are implicated in NLR regulation as well. In NSCLC, neutrophil extracellular traps downregulate the expression of lncRNA MIR503HG, activating the NF-κB/NLRP3 pathway to promote EMT and NSCLC metastasis.…”

Section: Innate Immune Pathways In Cancermentioning

confidence: 99%

Harnessing innate immune pathways for therapeutic advancement in cancer

Hu,

Sun,

Lin

et al. 2024

Sig Transduct Target Ther

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The innate immune pathway is receiving increasing attention in cancer therapy. This pathway is ubiquitous across various cell types, not only in innate immune cells but also in adaptive immune cells, tumor cells, and stromal cells. Agonists targeting the innate immune pathway have shown profound changes in the tumor microenvironment (TME) and improved tumor prognosis in preclinical studies. However, to date, the clinical success of drugs targeting the innate immune pathway remains limited. Interestingly, recent studies have shown that activation of the innate immune pathway can paradoxically promote tumor progression. The uncertainty surrounding the therapeutic effectiveness of targeted drugs for the innate immune pathway is a critical issue that needs immediate investigation. In this review, we observe that the role of the innate immune pathway demonstrates heterogeneity, linked to the tumor development stage, pathway status, and specific cell types. We propose that within the TME, the innate immune pathway exhibits multidimensional diversity. This diversity is fundamentally rooted in cellular heterogeneity and is manifested as a variety of signaling networks. The pro-tumor effect of innate immune pathway activation essentially reflects the suppression of classical pathways and the activation of potential pro-tumor alternative pathways. Refining our understanding of the tumor’s innate immune pathway network and employing appropriate targeting strategies can enhance our ability to harness the anti-tumor potential of the innate immune pathway and ultimately bridge the gap from preclinical to clinical application.

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“…CircAR-3, a circRNA derived from the androgen receptor gene, contributes to NLRP3 acetylation by KAT2B and NLRP3 inflammasome activation. Disturbing NLRP3 acetylation with the KAT2B inhibitor NS-1502 suppresses the progression of prostate cancer xenograft tumors [ 146 ].…”

Section: The Nlrp3 Inflammasome and Cancersmentioning

confidence: 99%

The Role of Post-Translational Modifications in Regulation of NLRP3 Inflammasome Activation

Xia

Jiang

Dong

et al. 2023

IJMS

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Pathogen-associated molecular patterns (PAMPs) and danger-associated molecular patterns (DAMPs) induce NLRP3 inflammasome activation, and subsequent formation of active caspase-1 as well as the maturation of interleukin-1β (IL-1β) and gasdermin D (GSDMD), mediating the occurrence of pyroptosis and inflammation. Aberrant NLRP3 inflammasome activation causes a variety of diseases. Therefore, the NLRP3 inflammasome pathway is a target for prevention and treatment of relative diseases. Recent studies have suggested that NLRP3 inflammasome activity is closely associated with its post-translational modifications (PTMs). This review focuses on PTMs of the components of the NLRP3 inflammasome and the resultant effects on regulation of its activity to provide references for the exploration of the mechanisms by which the NLRP3 inflammasome is activated and controlled.

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Disturbing NLRP3 acetylation and inflammasome assembly inhibits androgen receptor‐promoted inflammatory responses and prostate cancer progression

Cited by 14 publications

References 67 publications

Cuproptosis enhances docetaxel chemosensitivity by inhibiting autophagy via the DLAT/mTOR pathway in prostate cancer

Cuproptosis enhances docetaxel chemosensitivity by inhibiting autophagy via the DLAT/mTOR pathway in prostate cancer

Harnessing innate immune pathways for therapeutic advancement in cancer

The Role of Post-Translational Modifications in Regulation of NLRP3 Inflammasome Activation

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