Autophagic pathways as new targets for cancer drug development

Liu, Bo; Cheng, Yan; Liu, Qian; Bao, Jin; Yang, Jin Ming

doi:10.1038/aps.2010.118

Cited by 99 publications

(78 citation statements)

References 120 publications

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“…12,13 This defines the Janus role of autophagy and its ability to control a wide range of physiological processes, such as starvation, cell differentiation, cell survival, and death. 14 Finally, necroptosis is characterized by the relatively smallest number of regulators. Typically, necroptosis is modulated by c-Jun N-terminal kinase (JNK), apoptosis inducing factor (AIF), death-associated protein kinase (DAPK), and reactive oxygen species, [15][16][17][18] whereas in the apoptosis-incompetent cells, necroptosis is activated by death receptors and involves the RIP1 kinase.…”

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confidence: 99%

Resilience of death: intrinsic disorder in proteins involved in the programmed cell death

et al. 2013

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It is recognized now that intrinsically disordered proteins (IDPs), which do not have unique 3D structures as a whole or in noticeable parts, constitute a significant fraction of any given proteome. IDPs are characterized by an astonishing structural and functional diversity that defines their ability to be universal regulators of various cellular pathways. Programmed cell death (PCD) is one of the most intricate cellular processes where the cell uses specialized cellular machinery and intracellular programs to kill itself. This cell-suicide mechanism enables metazoans to control cell numbers and to eliminate cells that threaten the animal's survival. PCD includes several specific modules, such as apoptosis, autophagy, and programmed necrosis (necroptosis). These modules are not only tightly regulated but also intimately interconnected and are jointly controlled via a complex set of protein-protein interactions. To understand the role of the intrinsic disorder in controlling and regulating the PCD, several large sets of PCD-related proteins across 28 species were analyzed using a wide array of modern bioinformatics tools. This study indicates that the intrinsic disorder phenomenon has to be taken into consideration to generate a complete picture of the interconnected processes, pathways, and modules that determine the essence of the PCD. We demonstrate that proteins involved in regulation and execution of PCD possess substantial amount of intrinsic disorder. We annotate functional roles of disorder across and within apoptosis, autophagy, and necroptosis processes. Disordered regions are shown to be implemented in a number of crucial functions, such as protein-protein interactions, interactions with other partners including nucleic acids and other ligands, are enriched in post-translational modification sites, and are characterized by specific evolutionary patterns. We mapped the disorder into an integrated network of PCD pathways and into the interactomes of selected proteins that are involved in the p53-mediated apoptotic signaling pathway.

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confidence: 99%

Resilience of death: intrinsic disorder in proteins involved in the programmed cell death

et al. 2013

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“…ACD is marked with substantial mortification of cellular constituents, such as parts of the cytoplasm and intracellular organelles via intricate intracellular membrane/vesicle reformation and lysosomal hydrolysis [58][59][60]63]. Studies [58,59] have shown that ACD is essential for growth as well as stress antiphons.…”

Section: α-Mg and Autophagymentioning

confidence: 99%

“…Moreover, comparable to apoptosis, ACD is inhibited in malignant cancers. Studies have demonstrated that autophagy is triggered in reaction to γ irradiation and several anticancer remedies, specifically in apoptosis-deficient cells [58,63,64]. Numerous molecular and cell-signaling pathways have been incriminated in controlling autophagy.…”

Section: α-Mg and Autophagymentioning

confidence: 99%

The Pivotal Neuroinflammatory, Therapeutic and Neuroprotective Role of Alpha-Mangostin

Richard

Zheng

et al. 2017

J Neurol Res

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Alpha-mangostin (α-MG), one of the key xanthone derivatives, displays a multiplicity of curative qualities like antiinfective, anti-malarial, anticarcinogenic, antidiabetic actions as well as antioxidant properties. Furthermore, it has proven to have neuroprotective, hepatoprotective, and cardioprotective features, of which the anticarcinogenic action is the most auspicious. Additionally, several in vitro and in vivo analyses confirm that α-MG partakes in the major stages of tumor growth: initiation, promotion, and progression. Nevertheless, α-MG services as an inhibitory agent that modulate various enzymes involved in the metabolic activation and excretion of carcinogens, resistance to oxidative damage, and attenuation of inflammatory response. Numerous studies have also implicated α-MG in central nervous system (CNS) disorders, among which neuroinflammatory disorders and brain cancer are cardinal. Based on these initial studies on α-MG, we reviewed the pivotal role of α-MG in neuroinflammatory disorders.

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“…Previous studies have identified high expression levels of eEF2K in several types of cancer, and suggested that eEF2K may promote cell proliferation during nutrient starvation in these tumors (19)(20)(21). eEF2K has been considered as a potential cancer-therapeutic target, and the use of miRNA delivery agents for the treatment of different types of cancer has been investigated in previous clinical trials (1,(22)(23)(24)(25). Therefore, the identification of novel anticancer miRNAs capable of targeting eEF2K is of importance.…”

Section: Introductionmentioning

confidence: 99%

MicroRNA-877 acts as a tumor suppressor by directly targeting eEF2K in renal cell carcinoma

Shi

Liu

et al. 2015

Oncology Letters

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Abstract. MicroRNAs (miRNAs) are involved in tumorigenesis. However, little is known about their role in renal cell carcinoma (RCC). In the present study, the function of the miRNA miR-877 in RCC was investigated, and its expression levels in blood and paired RCC tissues were measured by reverse transcription-quantitative polymerase chain reaction (RT-qPCR). Bioinformatics analysis predicted eukaryotic elongation factor-2 kinase (eEF2K) to be the potential mRNA target of miR-877, which was verified by luciferase assay. The expression levels of eEF2K in RCC tissues were evaluated by western blot analysis and qPCR. The proliferation and migration abilities of RCC cells were measured by MTT and in vitro wound healing assays, respectively. The present results indicated that the expression levels of miR-877 were downregulated in blood and paired RCC tissues, whereas the expression levels of eEF2K were upregulated in RCC tissues. In addition, overexpression of miR-877 and knockdown of eEF2K significantly reduced the proliferation and migration abilities of RCC cells in vitro. Furthermore, miR-877 affected the eEF2K/eEF2 signaling pathway in these cells. In conclusion, the present study has demonstrated that miR-877 suppresses the proliferation and migration abilities of RCC cells by modulating the eEF2K/eEF2 signaling cascade. Therefore, miR-877 may be considered a potential biomarker for the diagnosis of RCC.

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Autophagic pathways as new targets for cancer drug development

Cited by 99 publications

References 120 publications

Resilience of death: intrinsic disorder in proteins involved in the programmed cell death

Resilience of death: intrinsic disorder in proteins involved in the programmed cell death

The Pivotal Neuroinflammatory, Therapeutic and Neuroprotective Role of Alpha-Mangostin

MicroRNA-877 acts as a tumor suppressor by directly targeting eEF2K in renal cell carcinoma

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