M‐<scp>COPA</scp>, a novel Golgi system disruptor, suppresses apoptosis induced by Shiga toxin

Hattori, Takayuki; Watanabe-Takahashi, Miho; Shiina, Isamu; Ohashi, Yoshimi; Dan, Shingo; Nishikawa, Kiyotaka; Yamori, Takao; Naito, Mikihiko

doi:10.1111/gtc.12386

Cited by 7 publications

(5 citation statements)

References 29 publications

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“…In addition, AMF-26 deactivates a mutant form of the endolysosomal Kit, leading to sensitizing carcinogenic mast cell to imatinib [57]. Finally, AMF-26 also prevents Shiga toxin-dependent apoptosis by decreasing its translocation into the Golgi apparatus [58].…”

Section: Arf1 and Its Inhibitors In Cancer Therapymentioning

confidence: 99%

Drugging the Small GTPase Pathways in Cancer Treatment: Promises and Challenges

Prieto-Domínguez

Parnell

Teng

2019

Cells

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Small GTPases are a family of low molecular weight GTP-hydrolyzing enzymes that cycle between an inactive state when bound to GDP and an active state when associated to GTP. Small GTPases regulate key cellular processes (e.g., cell differentiation, proliferation, and motility) as well as subcellular events (e.g., vesicle trafficking), making them key participants in a great array of pathophysiological processes. Indeed, the dysfunction and deregulation of certain small GTPases, such as the members of the Ras and Arf subfamilies, have been related with the promotion and progression of cancer. Therefore, the development of inhibitors that target dysfunctional small GTPases could represent a potential therapeutic strategy for cancer treatment. This review covers the basic biochemical mechanisms and the diverse functions of small GTPases in cancer. We also discuss the strategies and challenges of inhibiting the activity of these enzymes and delve into new approaches that offer opportunities to target them in cancer therapy.

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Section: Arf1 and Its Inhibitors In Cancer Therapymentioning

confidence: 99%

Drugging the Small GTPase Pathways in Cancer Treatment: Promises and Challenges

Prieto-Domínguez

Parnell

Teng

2019

Cells

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“…The expression profiling of treated and untreated THP-1 cells verifies that Stxs are responsible for genetic alterations (Leyva-Illades et al, 2010 ). Studies show that Stxs is associated with an elevated secretion of cytokines and other chemical mediators responsible for numerous diseases including cancer (DesRochers et al, 2015 ; Hattori et al, 2016 ). E. coli producing Stxs was isolated from cancer and diarrheagenic individuals (Chao et al, 2017 ).…”

Section: Introductionmentioning

confidence: 99%

Simulation Study of cDNA Dataset to Investigate Possible Association of Differentially Expressed Genes of Human THP1-Monocytic Cells in Cancer Progression Affected by Bacterial Shiga Toxins

et al. 2018

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Shiga toxin (Stxs) is a family of structurally and functionally related bacterial cytotoxins produced by Shigella dysenteriae serotype 1 and shigatoxigenic group of Escherichia coli that cause shigellosis and hemorrhagic colitis, respectively. Until recently, it has been thought that Stxs only inhibits the protein synthesis and induces expression to a limited number of genes in host cells, but recent data showed that Stxs can trigger several signaling pathways in mammalian cells and activate cell cycle and apoptosis. To explore the changes in gene expression induced by Stxs that have been shown in other systems to correlate with cancer progression, we performed the simulated analysis of cDNA dataset and found differentially expressed genes (DEGs) of human THP1-monocytic cells treated with Stxs. In this study, the entire data (treated and untreated replicates) was analyzed by statistical algorithms implemented in Bioconductor packages. The output data was validated by the k-fold cross technique using generalized linear Gaussian models. A total of 50 DEGs were identified. 7 genes including TSLP, IL6, GBP1, CD274, TNFSF13B, OASL, and PNPLA3 were considerably (<0.00005) related to cancer proliferation. The functional enrichment analysis showed 6 down-regulated and 1 up-regulated genes. Among these DEGs, IL6 was associated with several cancers, especially with leukemia, lymphoma, lungs, liver and breast cancers. The predicted regulatory motifs of these genes include conserved RELA, STATI, IRFI, NF-kappaB, PEND, HLF, REL, CEBPA, DI_2, and NFKB1 transcription factor binding sites (TFBS) involved in the complex biological functions. Thus, our findings suggest that Stxs has the potential as a valuable tool for better understanding of treatment strategies for several cancers.

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“…However, derivatives of BFA have shown anti-cancer activity against a plethora of cancer types, with most recent work targeting cervical, breast and hepatocellular cancers, with improved bioavailability [188][189][190][191][192]. Other methods to circumvent this issue are centred on improvement to drug delivery, such as that by Zhang et al who are using nanomicelles to improve the delivery of BFA [193][194][195][196]. Future work could combine these two strategies to bring BFA into the clinic.…”

Section: Conclusion and Future Perspectivesmentioning

confidence: 99%

Exploring Retrograde Trafficking: Mechanisms and Consequences in Cancer and Disease

Bingham,

McCarthy,

Buckley

2024

Traffic

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Retrograde trafficking (RT) orchestrates the intracellular movement of cargo from the plasma membrane, endosomes, Golgi or endoplasmic reticulum (ER)–Golgi intermediate compartment (ERGIC) in an inward/ER‐directed manner. RT works as the opposing movement to anterograde trafficking (outward secretion), and the two work together to maintain cellular homeostasis. This is achieved through maintaining cell polarity, retrieving proteins responsible for anterograde trafficking and redirecting proteins that become mis‐localised. However, aberrant RT can alter the correct location of key proteins, and thus inhibit or indeed change their canonical function, potentially causing disease. This review highlights the recent advances in the understanding of how upregulation, downregulation or hijacking of RT impacts the localisation of key proteins in cancer and disease to drive progression. Cargoes impacted by aberrant RT are varied amongst maladies including neurodegenerative diseases, autoimmune diseases, bacterial and viral infections (including SARS‐CoV‐2), and cancer. As we explore the intricacies of RT, it becomes increasingly apparent that it holds significant potential as a target for future therapies to offer more effective interventions in a wide range of pathological conditions.

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M‐COPA, a novel Golgi system disruptor, suppresses apoptosis induced by Shiga toxin

Cited by 7 publications

References 29 publications

Drugging the Small GTPase Pathways in Cancer Treatment: Promises and Challenges

Drugging the Small GTPase Pathways in Cancer Treatment: Promises and Challenges

Simulation Study of cDNA Dataset to Investigate Possible Association of Differentially Expressed Genes of Human THP1-Monocytic Cells in Cancer Progression Affected by Bacterial Shiga Toxins

Exploring Retrograde Trafficking: Mechanisms and Consequences in Cancer and Disease

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