Arrestins in Apoptosis

Kook, Seunghyi; Gurevich, Vsevolod V.; Gurevich, Eugenia V.

doi:10.1007/978-3-642-41199-1_16

Cited by 16 publications

(12 citation statements)

References 224 publications

(320 reference statements)

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“…The strong pro-apoptotic effect of GSK-3 inhibitors in extrinsic pathways triggered by death receptors has been well documented in our study and previous studies in other cancer cell types [34]. Selective knockdown of glycogen synthase kinase-3β but not glycogen synthase kinase-3α by RNA interference enhances TRAIL-induced cell death in pancreatic cancer cells [35].…”

Section: Discussionsupporting

confidence: 78%

GSK-3 inhibitors enhance TRAIL-mediated apoptosis in human gastric adenocarcinoma cells

Hsieh

Chiu

et al. 2018

PLoS ONE

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Resistance to tumor necrosis factor-related apoptosis-inducing ligand (TRAIL)-induced apoptosis has been reported in some cancer cells, including AGS human gastric adenocarcinoma cells. Reducing this resistance might shed light on the treatment of human gastric adenocarcinoma. In this study, we examined whether glycogen synthase kinase-3 (GSK-3) inhibitors can restore TRAIL responsiveness in gastric adenocarcinoma cells. The effect of two GSK-3 inhibitors, SB-415286, and LiCl, on apoptosis signaling of TRAIL in human gastric adenocarcinoma cell lines and primary gastric epithelial cells was analyzed. Both inhibitors can sensitize gastric adenocarcinoma cells, but not primary gastric epithelial cells, to TRAIL-induced apoptosis by increasing caspase-8 activity and its downstream signal transmission. Adding p53 siRNA can downregulate GSK-3 inhibitor-related sensitization to TRAIL-induced apoptosis and caspase-3 activity. GSK-3 inhibitors strongly activate the phosphorylation of JNK. Inhibition of JNK leads to earlier and more intense apoptosis, showing that the activation of JNK may provide anti-apoptotic equilibrium of pro-apoptotic cells. Our observations indicate that GSK-3 inhibitors can sentize AGS gastric adenocarcinoma cells to TRAIL-induced apoptosis. Therefore, in certain types of gastric adenocarcinoma, GSK-3 inhibitor might enhance the antitumor activity of TRAIL and mightbe a promising candidate for the treatment of certain types of gastric adenocarcinoma.

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Section: Discussionsupporting

confidence: 78%

GSK-3 inhibitors enhance TRAIL-mediated apoptosis in human gastric adenocarcinoma cells

Hsieh

Chiu

et al. 2018

PLoS ONE

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“…Kook et al (27) used mouse embryonic fibroblasts (MEFs) cells whereas the current study adopted HepG2 cells. β-arrestin has been demonstrated to have diverse roles via distinct mechanisms in various experimental models (22). In the present study, overexpression of β-arrestin2 using GFP-Arrb2 plasmids demonstrated that β-arrestin2 exerted anti-apoptotic role in HepG2 cells.…”

Section: Discussionsupporting

confidence: 54%

“…Recent studies have demonstrated that β-arrestins contribute to anti-apoptotic effects in apoptosis that is induced by a variety of stimuli (5,8,22). However, the role of β-arrestins in TRAIL-induced apoptosis remains unclear.…”

Section: Discussionmentioning

confidence: 99%

β-arrestin2 regulates TRAIL-induced HepG2 cell apoptosis via the Src-extracellular signal-regulated signaling pathway

Zhou

Lin

et al. 2016

Molecular Medicine Reports

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β-arrestins, including β-arrestin1 and β‑arrestin2, two ubiquitously expressed members of the arrestin family in various types of tissue, are adaptor proteins that modulate the desensitization and trafficking of seven membrane‑spanning receptors. Recently, β‑arrestins have been shown to bind to numerous signaling molecules, including c‑Src and mitogen‑activated protein kinase family members. In addition, accumulating evidence has suggested that β‑arrestins are involved in the anti‑apoptosis signaling pathway by associating with kinases, such as Akt and ERK, and altering their activities. However, the role of β‑arrestins in tumor necrosis factor‑related apoptosis‑inducing ligand (TRAIL)‑induced apoptosis remains unclear. In the present study, β‑arrestin2, but not β‑arrestin1, was observed to modulate TRAIL‑triggered HepG2 cell apoptosis by regulating activation of the Src‑extracellular signal‑regulated kinase (ERK) signaling pathway. Using overexpression and RNA interference experiments, β‑arrestin2 was demonstrated to prevent TRAIL‑induced HepG2 cell apoptosis. Additionally, β‑arrestin2 exerted an additive effect on TRAIL‑induced activation of Src and ERK. Furthermore, downregulating β‑arrestin2 expression attenuated the TRAIL‑induced activation of Src and ERK survival signaling and enhanced TRAIL‑induced apoptosis. PP2, a pharmacological inhibitor of Src, reduced activation of the Src‑ERK signaling pathway and enhanced TRAIL‑induced HepG2 cell apoptosis. Co-immunoprecipitation experiments demonstrated a physical association between β‑arrestin2 and Src, and TRAIL stimulation resulted in enhanced quantities of the β‑arrestin2/Src complex. A notable interaction was identified between β‑arrestin2 and death receptors (DR)4 and 5, but only in the presence of TRAIL stimulation. To the best of our knowledge, these findings are the first to demonstrate that β‑arrestin2 mediates TRAIL‑induced apoptosis by combing with DRs and Src, and regulates the activation of Src‑ERK signaling in HepG2 cells. It is hypothesized that the formation of a signaling complex comprising DR, β‑arrestin2 and Src is required for the action of TRAIL on HepG2 cell apoptosis, which provides a novel insight into analyzing the effects of β‑arrestin2 on protecting cells from TRAIL‑induced apoptosis.

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“…There are some indications that βArrs may trigger malignant signalling and cancer progression through activation of protein kinases (Src, MAPKs, PI3K), growth factor receptors, and transcription factors 5 , 7 , 13 . Furthermore, βArrs affect cell survival and can prevent GPCR-induced apoptosis 14 , 15 .…”

Section: Introductionmentioning

confidence: 99%

“…These are significant modulators of cellular growth and cancer cell migration, invasion, and metastasis [9][10][11][12] .There are some indications that βArrs may trigger malignant signalling and cancer progression through activation of protein kinases (Src, MAPKs, PI3K), growth factor receptors, and transcription factors 5,7,13 . Furthermore, βArrs affect cell survival and can prevent GPCR-induced apoptosis 14,15 .On the other hand, some studies indicate that βArr-mediated signalling reduces cell proliferation, migration, invasion, and metastasis, and induces apoptosis and an anti-cancer response pattern in some types of cancer [16][17][18] . They can facilitate cell death by mediating apoptotic signalling 17,18 .…”

mentioning

confidence: 99%

Overexpression of β-Arrestins inhibits proliferation and motility in triple negative breast cancer cells

Bostanabad

Noyan

Dedeoğlu

et al. 2021

Sci Rep

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Abstractβ-Arrestins (βArrs) are intracellular signal regulating proteins. Their expression level varies in some cancers and they have a significant impact on cancer cell function. In general, the significance of βArrs in cancer research comes from studies examining GPCR signalling. Given the diversity of different GPCR signals in cancer cell regulation, contradictory results are inevitable regarding the role of βArrs. Our approach examines the direct influence of βArrs on cellular function and gene expression profiles by changing their expression levels in breast cancer cells, MDA-MB-231 and MDA-MB-468. Reducing expression of βArr1 or βArr2 tended to increase cell proliferation and invasion whereas increasing their expression levels inhibited them. The overexpression of βArrs caused cell cycle S-phase arrest and differential expression of cell cycle genes, CDC45, BUB1, CCNB1, CCNB2, CDKN2C and reduced HER3, IGF-1R, and Snail. Regarding to the clinical relevance of our results, low expression levels of βArr1 were inversely correlated with CDC45, BUB1, CCNB1, and CCNB2 genes compared to normal tissue samples while positively correlated with poorer prognosis in breast tumours. These results indicate that βArr1 and βArr2 are significantly involved in cell cycle and anticancer signalling pathways through their influence on cell cycle genes and HER3, IGF-1R, and Snail in TNBC cells.

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Arrestins in Apoptosis

Cited by 16 publications

References 224 publications

GSK-3 inhibitors enhance TRAIL-mediated apoptosis in human gastric adenocarcinoma cells

GSK-3 inhibitors enhance TRAIL-mediated apoptosis in human gastric adenocarcinoma cells

β-arrestin2 regulates TRAIL-induced HepG2 cell apoptosis via the Src-extracellular signal-regulated signaling pathway

Overexpression of β-Arrestins inhibits proliferation and motility in triple negative breast cancer cells

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