The Disulfiram/Copper Complex Induces Autophagic Cell Death in Colorectal Cancer by Targeting ULK1

Hu, Yeting; Qian, Yuntao; Wei, Jingsun; Jin, Tian; Kong, Xianglong; Cao, Hongfeng; Ding, Kefeng

doi:10.3389/fphar.2021.752825

Cited by 28 publications

(18 citation statements)

References 25 publications

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“…Cuproptosis is a pattern of cell death newly defined by GOLUB et al (Tsvetkov et al, 2022), and its mechanism is distinct from other mechanisms known to regulate cell death. Some previous studies had demonstrated that unbalanced copper homeostasis could induce cell death and exert anti-tumor effects (Jiang et al, 2022), for instance, disulfiram/copper complexes can induce apoptosis in non-small cell lung cancer cells (Wu et al, 2018), induce autophagic death in colorectal cancer cells (Hu et al, 2021) and induce ROS-dependent apoptosis in malignant prostate cells (Safi et al, 2014). However, the current research on cuproptosis is still in its infancy.…”

Section: Discussionmentioning

confidence: 99%

Pan-cancer analyses confirmed the cuproptosis-related gene FDX1 as an immunotherapy predictor and prognostic biomarker

Zhang

Zeng²,

Guo³

et al. 2022

Front. Genet.

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Background: The latest research identified cuproptosis as an entirely new mechanism of cell death. However, as a key regulator in copper-induced cell death, the prognostic and immunotherapeutic value of FDX1 in pan-cancer remains unclear.Methods: Data from the UCSC Xena, GEPIA, and CPTAC were analyzed to conduct an inquiry into the overall differential expression of FDX1 across multiple cancer types. The expression of FDX1 in GBM, LUAD and HCC cell lines as well as their control cell lines was verified by RT-QPCR. The survival prognosis, clinical features, and genetic changes of FDX1 were also evaluated. Finally, the relationship between FDX1 and immunotherapy response was further explored through Gene Set Enrichment Analysis enrichment analysis, tumor microenvironment, immune cell infiltration, immune gene co-expression and drug sensitivity analysis.Results: The transcription and protein expression of FDX1 were significantly reduced in most cancer types and had prognostic value for the survival of certain cancer patients such as ACC, KIRC, HNSC, THCA and LGG. In some cancer types, FDX1 expression was also markedly correlated with the clinical characteristics, TMB, MSI, and antitumor drug susceptibility or resistance of different tumors. Gene set enrichment analysis showed that FDX1 was significantly associated with immune-related pathways. Moreover, the expression level of FDX1 was confirmed to be strongly correlated with immune cell infiltration, immune checkpoint genes, and immune regulatory genes to a certain extent.Conclusion: This study comprehensively explored the potential value of FDX1 as a prognostic and immunotherapeutic marker for pan-cancer, providing new direction and evidence for cancer therapy.

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Section: Discussionmentioning

confidence: 99%

Pan-cancer analyses confirmed the cuproptosis-related gene FDX1 as an immunotherapy predictor and prognostic biomarker

Zhang

Zeng²,

Guo³

et al. 2022

Front. Genet.

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Section: Crucial Signaling Pathways Of Rcd Subroutines In Cancermentioning

confidence: 99%

“…Hu et al reported that DSF combined with Cu could significantly inhibit the viability of CRC cells and trigger autophagic cell death instead of apoptosis via enhancing the ULK1 level. 221 Targeting PI3KC1/Akt/mTORC1. PI3KC1/Akt/mTORC1 signaling pathway has been considered as the pivotal regulator in various cell processes.…”

Section: Autophagy-dependent Cell Death Signaling Pathways In Cancermentioning

confidence: 99%

Regulated cell death (RCD) in cancer: key pathways and targeted therapies

Liao

Qin

et al. 2022

Sig Transduct Target Ther

310

154

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Regulated cell death (RCD), also well-known as programmed cell death (PCD), refers to the form of cell death that can be regulated by a variety of biomacromolecules, which is distinctive from accidental cell death (ACD). Accumulating evidence has revealed that RCD subroutines are the key features of tumorigenesis, which may ultimately lead to the establishment of different potential therapeutic strategies. Hitherto, targeting the subroutines of RCD with pharmacological small-molecule compounds has been emerging as a promising therapeutic avenue, which has rapidly progressed in many types of human cancers. Thus, in this review, we focus on summarizing not only the key apoptotic and autophagy-dependent cell death signaling pathways, but the crucial pathways of other RCD subroutines, including necroptosis, pyroptosis, ferroptosis, parthanatos, entosis, NETosis and lysosome-dependent cell death (LCD) in cancer. Moreover, we further discuss the current situation of several small-molecule compounds targeting the different RCD subroutines to improve cancer treatment, such as single-target, dual or multiple-target small-molecule compounds, drug combinations, and some new emerging therapeutic strategies that would together shed new light on future directions to attack cancer cell vulnerabilities with small-molecule drugs targeting RCD for therapeutic purposes.

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“…Recently, there is a study has shown that ULK1 is the most frequently mutated gene in The Cancer Genome Atlas (TCGA)-colorectal adenocarcinoma dataset, implying that ULK1 and its regulatory network may be closely related to colorectal carcinogenesis ( 14 ). Notably, the upregulation of ULK1 significantly induces autophagy-dependent cell death in RKO human CRC cells, which exerts excellent antiproliferative potency ( 15 ).…”

Section: Crucial Pathways For Autophagy Regulation In Crcmentioning

confidence: 99%

Deconvoluting the complexity of autophagy in colorectal cancer: From crucial pathways to targeted therapies

Qiang

Liu²,

Wang³

et al. 2022

Front. Oncol.

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Colorectal cancer (CRC) is a common gastrointestinal tumor with a high degree of malignancy, and most clinical cases are diagnosed at an advanced stage, which has unfortunately missed an opportunity for surgery; therefore, elucidation of the crucial pathways of CRC development and discovery of targeted therapeutic strategies should be anticipated. Autophagy, which is an evolutionarily highly conserved catabolic process, may promote tumorigenesis and development of CRC. On the contrary, autophagy can trigger programmed cell death to inhibit CRC progression. Correspondingly, several targeted therapeutic strategies have been reported in CRC, including small-molecule compounds, polypeptides, non-coding RNAs, photodynamic, and adjuvant therapies. Thus, in this review, we focus on summarizing the crucial pathways of autophagy in CRC, and further discuss the current therapeutic strategies targeting autophagy. Together, these findings may shed light on the key regulatory mechanisms of autophagy and provide more promising therapeutic approaches for the future CRC therapies.

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The Disulfiram/Copper Complex Induces Autophagic Cell Death in Colorectal Cancer by Targeting ULK1

Cited by 28 publications

References 25 publications

Pan-cancer analyses confirmed the cuproptosis-related gene FDX1 as an immunotherapy predictor and prognostic biomarker

Pan-cancer analyses confirmed the cuproptosis-related gene FDX1 as an immunotherapy predictor and prognostic biomarker

Regulated cell death (RCD) in cancer: key pathways and targeted therapies

Deconvoluting the complexity of autophagy in colorectal cancer: From crucial pathways to targeted therapies

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