Siva-1 emerges as a tissue-specific oncogene beyond its classic role of a proapoptotic gene

Vachtenheim, J; Lischke, Robert

doi:10.2147/ott.s173001

Cited by 7 publications

(6 citation statements)

References 42 publications

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“…lV, lentivirus; Mdr1, multidrug resistance 1; MrP1, multidrug resistance protein 1; nc, negative control; Vcr, vincristine. The Siva-1 protein serves a crucial role in certain extrinsic and intrinsic apoptosis signaling pathways (16). However, Siva-1 has been demonstrated to serve contradictory roles in previous studies.…”

Section: Discussionmentioning

confidence: 99%

“…gene is located on chromosome 14 (14), a region which is often targeted for chromosomal translocation. Previous studies have demonstrated that Siva-1 arrests apoptosis and facilitates cancer development in osteosarcoma, hepatocellular carcinoma and non-small cell lung cancer (15)(16)(17)(18). However, the molecular function of Siva-1 regulating multidrug resistant in gastric cancer currently remains uncertain as previous studies have presented confusing and ambiguous results (16), which has prompted further investigation into both its function and associated signaling pathway.…”

Section: Siva-1 Regulates Multidrug Resistance Of Gastric Cancer By Targeting Mdr1 and Mrp1 Via The Nf-κb Pathwaymentioning

confidence: 99%

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Siva‑1 regulates multidrug resistance of gastric cancer by targeting MDR1 and MRP1 via the NF‑κB pathway

Kong

Deng

et al. 2020

Mol Med Rep

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Siva-1 is a well-known anti-apoptosis protein that serves a role in multiple types of cancer cells. However, whether Siva-1 affects multidrug resistance via the nF-κB pathway in gastric cancer is currently unknown. The present study aimed to determine the possible involvement of Siva-1 in gastric cancer anticancer drug resistance in vitro. a vincristine (Vcr)-resistant KaTo iii/Vcr gastric cancer cell line with stable Siva-1 overexpression was established. The protein expression levels of Siva-1, nF-κB, multidrug resistance 1 (Mdr1) and multidrug resistance protein 1 (MrP1) were detected via western blotting. The effect of Siva-1 overexpression on anticancer drug resistance was assessed by measuring the 50% inhibitory concentration of KATO III/VCR cells to VCR, 5-fluorouracil and doxorubicin. The rate of doxorubicin efflux and apoptosis were detected by flow cytometry. additionally, colony formation, wound healing and Transwell assays were used to detect the proliferation, migration and invasion of cells, respectively. The results of the current study revealed that the Siva-1-overexpressed KATO III/VCR gastric cancer cells exhibited a significantly decreased sensitivity to VCR, 5-fluorouracil and doxorubicin. The results of flow cytometry revealed that the percentage of apoptotic cells decreased following overexpression of Siva-1. The colony formation assay demonstrated that cell growth and proliferation were significantly promoted by Siva-1 overexpression. additionally, Siva-1 overexpression increased the migration and invasion of KaTo iii/Vcr cells in vitro. Western blot analysis determined that Siva-1 overexpression increased nF-κB, Mdr1 and MrP1 levels. The current study demonstrated that overexpression of Siva-1, which functions as a regulator of Mdr1 and MrP1 gene expression in gastric cancer cells via promotion of nF-κB expression, inhibited the sensitivity of gastric cancer cells to certain chemotherapies. These data provided novel insight into the molecular mechanisms of gastric cancer, and may be of significance for the clinical diagnosis and therapy of patients with gastric cancer.

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Section: Discussionmentioning

confidence: 99%

Section: Siva-1 Regulates Multidrug Resistance Of Gastric Cancer By Targeting Mdr1 and Mrp1 Via The Nf-κb Pathwaymentioning

confidence: 99%

Siva‑1 regulates multidrug resistance of gastric cancer by targeting MDR1 and MRP1 via the NF‑κB pathway

Kong

Deng

et al. 2020

Mol Med Rep

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“…TARBP2 and YBX-1 are central regulators of DICER/Ago2 mediated miRNAs processing in GBM (Frohn et al, 2012; Wu et al, 2015), consistent with the particular heightened role of epigenetic mechanisms, including those mediated by miRNAs and non-coding RNAs, play in GBM plasticity (Balci et al, 2016; Li et al, 2016; Peng et al, 2018; Zhang et al, 2015). SIVA1 is an E3 ubiquitin ligase that promotes degradation of the tumor suppressor and cell cycle checkpoint protein ARF, which in turn downregulates p53 (Vachtenheim et al, 2018; Van Nostrand et al, 2015; Wang et al, 2013). Loss of p53 and ARF are classical features of glioblastoma (Kim et al, 2012; Mao et al, 2012; Zheng et al, 2008).…”

Section: Resultsmentioning

confidence: 99%

Single-cell based elucidation of molecularly-distinct glioblastoma states and drug sensitivity

Ding

Burgenske

Zhao

et al. 2019

Preprint

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Glioblastoma heterogeneity and plasticity remain controversial, with proposed subtypes representing the average of highly heterogeneous admixtures of independent transcriptional states. Single-cell, protein-activity-based analysis allowed full quantification of >6,000 regulatory and signaling proteins, thus providing a previously unattainable single-cell characterization level. This helped identify four novel, molecularly distinct subtypes that successfully harmonize across multiple GBM datasets, including previously published bulk and single-cell profiles and single cell profiles from seven orthotopic PDX models, representative of prior subtype diversity. GBM is thus characterized by the plastic coexistence of single cells in two mutually-exclusive developmental lineages, with additional stratification provided by their proliferative potential. Consistently, all previous subtypes could be recapitulated by single-cell mixtures drawn from newly identified states. Critically, drug sensitivity was predicted and validated as highly state-dependent, both in single-cell assays from patient-derived explants and in PDX models, suggesting that successful treatment requires combinations of multiple drugs targeting these distinct tumor states. Significance We propose a new, 4-subtype GBM classification, which harmonizes across bulk and single-cell datasets. Single-cell mixtures from these subtypes effectively recapitulate all prior classifications, suggesting that the latter are a byproduct of GBM heterogeneity. Finally, we predict single-cell level activity of three clinically-relevant drugs, and validate them in patient-derived explant.

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“…Beyond its role in apoptosis, SIVA-1 also regulates other cellular processes, such as cellular migration ( Li et al, 2011 ; Ma et al, 2017 ), autophagy ( Van Nostrand et al, 2015 ), and proliferation ( Ma et al, 2017 ; Liu et al, 2020 ). In cancer studies SIVA-1 has been found to have a role as pro- or anti-malignant factor, depending on cellular context ( Vachtenheim et al, 2018 ).…”

Section: Introductionmentioning

confidence: 99%

FAIM-L - SIVA-1: Two Modulators of XIAP in Non-Apoptotic Caspase Function

Coccia

Solé

Comella

2022

Front. Cell Dev. Biol.

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Apoptosis is crucial for the correct development of the nervous system. In adulthood, the same protein machinery involved in programmed cell death can control neuronal adaptiveness through modulation of synaptic pruning and synaptic plasticity processes. Caspases are the main executioners in these molecular pathways, and their strict regulation is essential to perform neuronal remodeling preserving cell survival. FAIM-L and SIVA-1 are regulators of caspase activation. In this review we will focus on FAIM-L and SIVA-1 as two functional antagonists that modulate non-apoptotic caspase activity in neurons. Their participation in long-term depression and neurite pruning will be described in base of the latest studies performed. In addition, the association of FAIM-L non-apoptotic functions with the neurodegeneration process will be reviewed.

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Siva-1 emerges as a tissue-specific oncogene beyond its classic role of a proapoptotic gene

Cited by 7 publications

References 42 publications

Siva‑1 regulates multidrug resistance of gastric cancer by targeting MDR1 and MRP1 via the NF‑κB pathway

Siva‑1 regulates multidrug resistance of gastric cancer by targeting MDR1 and MRP1 via the NF‑κB pathway

Single-cell based elucidation of molecularly-distinct glioblastoma states and drug sensitivity

FAIM-L - SIVA-1: Two Modulators of XIAP in Non-Apoptotic Caspase Function

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