The role and mechanism of β‑arrestins in cancer invasion and metastasis (Review)

Song, Qing; Ji, Qing; Li, Qi

doi:10.3892/ijmm.2017.3288

Cited by 50 publications

(48 citation statements)

References 120 publications

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“…For example, in murine asthma models, diseasepromoting PAR-2 proinflammatory signaling is dependent on b-arrestin-2, whereas G-protein-dependent signaling is beneficial (57,58). Several in vitro, in vivo, and human patient data suggest that dysregulation of b-arrestin expression, localization, and/or phosphorylation is associated with increased migration and invasion and ultimately poorer outcomes in various types of cancer (59,60). This may be attributed not only to direct tumorigenic signaling through b-arrestin but also other selective pathways of PAR-2 signaling.…”

Section: Protease-stimulated Par-2 Activation and Signalingmentioning

confidence: 99%

Membrane-Anchored Serine Proteases and Protease-Activated Receptor-2–Mediated Signaling: Co-Conspirators in Cancer Progression

2019

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Pericellular proteolysis provides a significant advantage to developing tumors through the ability to remodel the extracellular matrix, promote cell invasion and migration, and facilitate angiogenesis. Recent advances demonstrate that pericellular proteases can also communicate directly to cells by activation of a unique group of transmembrane G-protein-coupled receptors (GPCR) known as proteaseactivated receptors (PAR). In this review, we discuss the specific roles of one of four mammalian PARs, namely PAR-2, which is overexpressed in advanced stage tumors and is activated by trypsin-like serine proteases that are highly expressed or otherwise dysregulated in many cancers. We highlight recent insights into the ability of different protease agonists to bias PAR-2 signaling and the newly emerging evidence for an interplay between PAR-2 and membrane-anchored serine proteases, which may co-conspire to promote tumor progression and metastasis. Interfering with these pathways might provide unique opportunities for the development of new mechanism-based strategies for the treatment of advanced and metastatic cancers.

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Section: Protease-stimulated Par-2 Activation and Signalingmentioning

confidence: 99%

Membrane-Anchored Serine Proteases and Protease-Activated Receptor-2–Mediated Signaling: Co-Conspirators in Cancer Progression

2019

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“…These data corroborate, at least in part, our finding although they should be considered cautiously, since gene expression levels The link between GPCR/β-arrestins complexes and cancer is an established concept (41) and seems to be result of sustained intracellular signaling occurring upon dysregulation of intracellular β-arrestin protein levels (42). These molecules were associated with drug resistance of breast (43) and lung cancer cells (44), cancer cell migration and invasion (45), tumor progression (46) and metastasis (47), as well as a number of other tumors (48). Thus, β-arrestins were proposed as a target for therapeutic strategies (49).…”

Section: Discussionmentioning

confidence: 99%

β-arrestin 2 Is a Prognostic Factor for Survival of Ovarian Cancer Patients Upregulating Cell Proliferation

et al. 2020

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“…␤-Arrestin-1 has been shown to be a scaffolding protein that brings numerous proteins together to promote their concerted interactions (12)(13)(14). Moreover, existing evidence suggests that ␤-arrestin-1 acts as a modulator of a variety of cellular processes, such as proliferation, differentiation, and apoptosis, that are also widely known to be regulated by the glucocorticoid receptor (15,16). Therefore, we queried whether ␤-arrestin-1 could associate with GR by performing a co-immunoprecipitation assay in A549 lung adenocarcinoma cells, which were chosen as a classic glucocorticoid-responsive cell line.…”

Section: ␤-Arrestin-1 Associates In a Complex With The Glucocorticoidmentioning

confidence: 99%

β-Arrestin-1 inhibits glucocorticoid receptor turnover and alters glucocorticoid signaling

Petrillo

Oakley

Cidlowski

2019

Journal of Biological Chemistry

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Glucocorticoids are among the most widely used drugs to treat many autoimmune and inflammatory diseases. Although much research has been focused on investigating glucocorticoid activity, it remains unclear how glucocorticoids regulate distinct processes in different cells. Glucocorticoids exert their effects through the glucocorticoid receptor (GR), which, upon glucocorticoid binding, interacts with regulatory proteins, affecting its activity and function. These protein-protein interactions are necessary for the resolution of glucocorticoid-dependent physiological and pharmacological processes. In this study, we discovered a novel protein interaction between the glucocorticoid receptor and ␤-arrestin-1, a scaffold protein with a well-established role in G protein-coupled receptor signaling. Using coimmunoprecipitation and in situ proximity ligation assays in A549 cells, we observed that ␤-arrestin-1 and unliganded GR interact in the cytoplasm and that, following glucocorticoid binding, the protein complex is found in the nucleus. We show that siRNA-mediated ␤-arrestin-1 knockdown alters GR protein turnover by up-regulating the E3 ubiquitin ligase Pellino-1, which catalyzes GR ubiquitination and thereby marks the receptor for proteasomal degradation. The enhanced GR turnover observed in ␤-arrestin-1deficient cells limits the duration of the glucocorticoid response on GR target genes. These results demonstrate that ␤-arrestin-1 is a crucial player for the stability of the glucocorticoid receptor. The GR/␤-arrestin-1 interaction uncovered here may help unravel mechanisms that contribute to the cell type-specific activities of glucocorticoids. Glucocorticoids (GCs) 2 are lifesaving drugs that are widely prescribed in the treatment of inflammatory diseases and other cro ARTICLE

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The role and mechanism of β‑arrestins in cancer invasion and metastasis (Review)

Cited by 50 publications

References 120 publications

Membrane-Anchored Serine Proteases and Protease-Activated Receptor-2–Mediated Signaling: Co-Conspirators in Cancer Progression

Membrane-Anchored Serine Proteases and Protease-Activated Receptor-2–Mediated Signaling: Co-Conspirators in Cancer Progression

β-arrestin 2 Is a Prognostic Factor for Survival of Ovarian Cancer Patients Upregulating Cell Proliferation

β-Arrestin-1 inhibits glucocorticoid receptor turnover and alters glucocorticoid signaling

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