Inhibition of Proteasome Activity Induces Aggregation of IFIT2 in the Centrosome and Enhances IFIT2-Induced Cell Apoptosis

Chen, Limin; Liu, Shuyuan; Xu, Fen; Kong, Yun-Yuan; Wan, Lei; Zhang, Yong‐Lu; Zhang, Zhanglin

doi:10.7150/ijbs.17236

Cited by 28 publications

(28 citation statements)

References 28 publications

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“…Wang et al have suggested that the long non-coding RNA LINC00161 can sensitize the osteosarcoma cells to cisplatin-induced apoptosis by regulating the miR-645-IFIT2 axis [22]. A recent study has also revealed that the inhibition of proteasome activity blocks the degradation of IFIT2 and promotes the aggregation of IFIT2 in the centrosome, which in turn induces cell apoptosis [8]. Therefore, the contribution of IFIT2 in promotion of cell apoptosis might encompass an anti-tumor mechanism for the translational regulation involving in cancerous transformation and inhibition of tumor colonization, and thus it could be used as a potential target for cancer therapeutics.…”

Section: Discussionmentioning

confidence: 99%

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Decreased IFIT2 Expression Promotes Gastric Cancer Progression and Predicts Poor Prognosis of the Patients

Chen

Zhai

Zheng

et al. 2017

Cell Physiol Biochem

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Background/Aims: The status of interferon (IFN) signaling pathway has been shown to be closely associated with the response of immune checkpoint blockade therapy against advanced human cancers. IFN-induced protein with tetratricopeptide repeats 2 (IFIT2), also known as IFN-stimulated gene 54 (ISG54), is one of the most highly responsive ISGs, which can inhibit the proliferation and migration of cancer cells, and regulate viral replication, resulting in anti-cancer and anti-viral effects. In the present study, we aimed to investigate the role of IFIT2 in human gastric cancer. Methods: Immunohistochemistry assay was used to investigate the correlation between the IFIT2 expression in cancer tissues and clinical parameters of gastric cancer patients. Knockdown of IFIT2 was performed using RNAi to assess the role of IFIT2 in the regulation of biological behaviors in human gastric cancer cell lines. Results: IFIT2 expression in gastric cancer tissues was significantly associated with tumor stage and postoperative prognoses of the patients. Moreover, decreased IFIT2 expression in human gastric cancer cell lines SGC-7901 and AGS significantly increased the cell viability, cell migration and the ratios of cells in S phase. Conclusion: Our present study demonstrated that the decreased IFIT2 expression could promote the gastric cancer progression and predict poor therapeutic outcomes of the patients.

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Section: Discussionmentioning

confidence: 99%

“…It can inhibit the proliferation and migration of cancer cells and regulate viral replication, exerting an anti-cancer as well as anti-viral effect mediated by IFN [5-8]. The expression of IFIT2 can also promote cell death via apoptosis through a mitochondrial pathway dependent on Bcl2 [9].…”

Section: Introductionmentioning

confidence: 99%

Decreased IFIT2 Expression Promotes Gastric Cancer Progression and Predicts Poor Prognosis of the Patients

Chen

Zhai

Zheng

et al. 2017

Cell Physiol Biochem

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“…Intriguingly, IFIT-family proteins display distinct functions in apoptosis. The negative association of IFIT2 with tumor malignancy is likely due to its pro-apoptotic activity (Stawowczyk et al, 2011;Chen et al, 2017). Ectopic IFIT2 overexpression induced the activation of caspase-3 and disturbed the plasma membrane asymmetry and permeability, which is a basic characteristic feature of apoptosis (Stawowczyk et al, 2011;Lai et al, 2013;Feng et al, 2014).…”

Section: Ifits In Apoptosismentioning

confidence: 99%

“…In addition, IFIT2 was associated with the mediator of IRF3 activation (MITA) and regulated apoptotic cell death via the mitochondrial pathway (Stawowczyk et al, 2011). Inhibition of proteasome-mediated degradation of IFIT2 led to the aggregation of IFIT2 in the perinuclear region and promoted apoptosis (Chen et al, 2017). Derepression of IFIT2 made the cells prone to apoptotic death induced by external stimuli such as chemotherapeutic drugs and serum starvation (Feng et al, 2014;Wang et al, 2016).…”

Section: Ifits In Apoptosismentioning

confidence: 99%

“…Derepression of IFIT2 made the cells prone to apoptotic death induced by external stimuli such as chemotherapeutic drugs and serum starvation (Feng et al, 2014;Wang et al, 2016). IFIT2-mediated apoptosis was not dependent on the DNA damage response (Chen et al, 2017;Ohsugi et al, 2017). Rather, IFIT2 induced apoptosis by regulating the balance between pro-and anti-apoptotic Bcl-2 family proteins, which altered the permeability of the mitochondrial membrane (Tait and Green, 2010;Stawowczyk et al, 2011).…”

Section: Ifits In Apoptosismentioning

confidence: 99%

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Emerging Functions of Human IFIT Proteins in Cancer

Pidugu

et al. 2019

Front. Mol. Biosci.

115

105

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Interferon-induced protein with tetratricopeptide repeats (IFIT) genes are prominent interferon-stimulated genes (ISGs). The human IFIT gene family consists of four genes named IFIT1, IFIT2, IFIT3, and IFIT5. The expression of IFIT genes is very low in most cell types, whereas their expression is greatly enhanced by interferon treatment, viral infection, and pathogen-associated molecular patterns (PAMPs). The proteins encoded by IFIT genes have multiple tetratricopeptide repeat (TPR) motifs. IFIT proteins do not have any known enzymatic roles. However, they execute a variety of cellular functions by mediating protein-protein interactions and forming multiprotein complexes with cellular and viral proteins through their multiple TPR motifs. The versatile tertiary structure of TPR motifs in IFIT proteins enables them to be involved in distinct biological functions, including host innate immunity, antiviral immune response, virus-induced translation initiation, replication, double-stranded RNA signaling, and PAMP recognition. The current understanding of the IFIT proteins and their role in cellular signaling mechanisms is limited to the antiviral immune response and innate immunity. However, recent studies on IFIT protein functions and their involvement in various molecular signaling mechanisms have implicated them in cancer progression and metastasis. In this article, we focused on critical molecular, biological and oncogenic functions of human IFIT proteins by reviewing their prognostic significance in health and cancer. Research suggests that IFIT proteins could be novel therapeutic targets for cancer therapy.

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STAT1/IFIT2 signaling pathway is involved in PD-L1-mediated epithelial-to-mesenchymal transition in human esophageal cancer

et al. 2022

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Background We have previously reported significant change of epithelial to mesenchymal transition (EMT) phenotype of Eca-109 cells upon PD-L1 operation, and the cytoplasmic domain of PD-L1 played an essential role in promoting EMT of esophageal cancer cells. However, the underlying mechanism of how PD-L1 regulated EMT in esophageal cancer remained unclear. Methods The overexpression and knockdown expression models of PD-L1 and IFIT2 were established by using lenti-virus transfection and RNAi method. Western blotting, qRT-PCR, CCK8 assay, transwell assay and wound healing assay were chosen to investigate their impact on the cells. The expression levels of IFIT2 and EMT markers in esophageal cancer tissues were examined by immunohistochemical staining. The rescue experiments were further applied to investigate the role of STAT1/IFIT2 signal pathway in the PD-L1-mediated EMT. Luciferase reporter assays were performed to examine the IFIT2 promoter activities upon knockdown expression of PD-L1 to identify the putative targeted region of IFIT2 promoter. Results The STAT1/IFIT2 signal pathway was activated when PD-L1 was knockdown in human esophageal cancer cells. Decreased IFIT2 expression significantly increased the cellular abilities of viability, invasion and migration by using RNAi method in human esophageal cancer cells. Decreased IFIT2 expression in esophageal cancer tissues significantly correlated with EMT status, and could be used as an independent prognostic predictor for the patients. Rescue experiments in PD-L1 knockdown cells further confirmed that STAT1/IFIT2 pathway was involved in the PD-L1 mediated EMT of esophageal cancer cells. Moreover, the luciferase reporter assay also confirmed that in esophageal cancer cells, the promoter region of IFIT2 (-3K~-1K) remains more active in PD-L1 knockdown expression cells compared with controls. Conclusion Our present work reveals a novel mechanism of how PD-L1 regulates EMT of cancer cells, namely STAT1/IFIT2 signal pathway is required in PD-L1 mediated EMT in human esophageal cancer.

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Inhibition of Proteasome Activity Induces Aggregation of IFIT2 in the Centrosome and Enhances IFIT2-Induced Cell Apoptosis

Cited by 28 publications

References 28 publications

Decreased IFIT2 Expression Promotes Gastric Cancer Progression and Predicts Poor Prognosis of the Patients

Decreased IFIT2 Expression Promotes Gastric Cancer Progression and Predicts Poor Prognosis of the Patients

Emerging Functions of Human IFIT Proteins in Cancer

STAT1/IFIT2 signaling pathway is involved in PD-L1-mediated epithelial-to-mesenchymal transition in human esophageal cancer

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