β-Arrestin1 mediates hMENA expression and ovarian cancer metastasis

Purayil, Hamsa Thayele; Daaka, Yehia

doi:10.1073/pnas.1802643115

Cited by 6 publications

(4 citation statements)

References 21 publications

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“…Additional studies demonstrated that overexpression of βarr1 inhibited the growth and migration of TNBC cell lines in an AMPK-dependent fashion (Son et al, 2019), suggesting that βarr1 acts as a tumor suppressor in TNBC. In contrast to this finding, several other studies reported that βarr1 expression is upregulated in different types of cancer (Purayil and Daaka, 2018; Zecchini et al, 2014). These data suggest that the ability of βarr1 to promote or suppress cancer cell growth and metastasis may depend on the type of cancer under investigation.…”

Section: Breastcontrasting

confidence: 74%

β−Arrestins: Structure, Function, Physiology, and Pharmacological Perspectives

Wess¹,

Oteng²,

Rivera‐Gonzalez³

et al. 2023

Pharmacol Rev

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The two β-arrestins, β-arrestin-1 and -2 (systematic names: arrestin-2 and -3, respectively), are multifunctional intracellular proteins that regulate the activity of a very large number of cellular signaling pathways and physiological functions. The two proteins were discovered for their ability to disrupt signaling via G protein-coupled receptors (GPCRs) via binding to the activated receptors. However, it is now well recognized that both β-arrestins can also act as direct modulators of numerous cellular processes via either GPCR-dependent orindependent mechanisms. Recent structural, biophysical, and biochemical studies have provided novel insights into how β-arrestins bind to activated GPCRs and downstream effector proteins.Studies with β-arrestin mutant mice have identified numerous physiological and pathophysiological processes regulated by β-arrestin-1 and/or -2. Following a short summary of recent structural studies, this review will primarily focus on β-arrestin-regulated physiological functions, with particular focus on the central nervous system and the roles of β-arrestins in carcinogenesis and key metabolic processes including the maintenance of glucose and energy homeostasis. This review will also highlight potential therapeutic implications of these studies and discuss strategies that could prove useful for targeting specific β-arrestin-regulated signaling pathways for therapeutic purposes.

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Section: Breastcontrasting

confidence: 74%

β−Arrestins: Structure, Function, Physiology, and Pharmacological Perspectives

Wess¹,

Oteng²,

Rivera‐Gonzalez³

et al. 2023

Pharmacol Rev

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“…In this context, our recent findings highlighted b-arr1 as the center of a regulatory complex at the interface of ET A R signaling and invadopodia, in fine-tuning SOC cell invasion and metastasis (Rosanò and Bagnato, 2019). As a pri-mary component of a core scaffold to direct spatiotemporal specificity of multi-protein complexes, b-arr1 controls the reorganization of the actin cytoskeleton to favor ECM degradation and transendothelial migration process (Semprucci et al, 2016;Di Modugno et al, 2012, 2018Purayil and Daaka, 2018;Chellini et al, 2019). As previously reported, ILK might function as a bridge between proteolytic and adhesion signaling, since it resides in the same pathway of integrins to invadopodiumassociated ECM degradation (Sakurai-Yageta et al, 2008), making ILK as an attractive signaling molecule to dissect in ET-1dependent invadopodium activity.…”

Section: Discussionmentioning

confidence: 98%

“…RhoC is the main Rho GTPase regulated by b-arr1 through the interaction with PDZ-RhoGEF and the actin regulator hMENA/hMENADv6. The activity and the spatial distribution of RhoC represents a critical route by which the tumor cells control the recruitments of cortactin, TKS5, and MMPs in the formation of non-degradative invadopodium precursors, and the spatial restriction of cofilin activity, starting the maturation process (Semprucci et al, 2016;Di Modugno et al, 2018;Purayil and Daaka, 2018), further highlighting the interaction network of b-arr proteins in controlling cytoskeleton dynamics (Masi et al, 2020;DeFea, 2013).…”

Section: Introductionmentioning

confidence: 99%

Endothelin-1 drives invadopodia and interaction with mesothelial cells through ILK

et al. 2021

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Endothelin-1 drives invadopodia and interaction with mesothelial cells through ILK Graphical abstract Highlights d ET A R/b-arr1 and ILK activate Rac3 GTPase, PAK1, and cofilin pathways through bPIX d ET A R/ILK/b-arr1/Rac3 regulates invadopodia, ECM proteolysis, and cell invasion d ET A R/b-arr1/ILK facilitates SOC/mesothelial cells interactions d Ambrisentan inhibits in vivo adhesion and metastatic spread of SOC cells

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“…One study showed ß-arrestin1 could be used as a plasma biomarker to differentiate certain types of lung cancers ( El-Khoury et al., 2018 ). Ovarian cancer metastasis has also been reported to be mediated by ß-arrestin1 ( Purayil and Daaka, 2018 ). Studies also suggest ß-arrestin2 as a prognosis marker for colorectal cancer ( Ren et al., 2018 ) and a promoter of lymph node metastasis in non–small cell lung cancer ( Cong et al., 2017 ).…”

Section: Effects Of ß-Arrestin On Diseasementioning

confidence: 99%

Therapeutic Potential of Targeting ß-Arrestin

et al. 2019

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ß-arrestins are multifunctional proteins that modulate heptahelical 7 transmembrane receptors, also known as G protein-coupled receptors (GPCRs), a superfamily of receptors that regulate most physiological processes. ß-arrestin modulation of GPCR function includes termination of G protein-dependent signaling, initiation of ß-arrestin-dependent signaling, receptor trafficking to degradative or recycling pathways, receptor transactivation, transcriptional regulation, and localization of second messenger regulators. The pleiotropic influence ß-arrestins exert on these receptors regulates a breadth of physiological functions, and additionally, ß-arrestins are involved in the pathophysiology of numerous and wide-ranging diseases, making them prime therapeutic targets. In this review, we briefly describe the mechanisms by which ß-arrestins regulate GPCR signaling, including the functional cellular mechanisms modulated by ß-arrestins and relate this to observed pathophysiological responses associated with ß-arrestins. We focus on the role for ß-arrestins in transducing cell signaling; a pathway that is complementary to the classical G protein-coupling pathway. The existence of these GPCR dual signaling pathways offers an immense therapeutic opportunity through selective targeting of one signaling pathway over the other. Finally, we will consider several mechanisms by which the potential of dual signaling pathway regulation can be harnessed and the implications for improved disease treatments.

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β-Arrestin1 mediates hMENA expression and ovarian cancer metastasis

Cited by 6 publications

References 21 publications

β−Arrestins: Structure, Function, Physiology, and Pharmacological Perspectives

β−Arrestins: Structure, Function, Physiology, and Pharmacological Perspectives

Endothelin-1 drives invadopodia and interaction with mesothelial cells through ILK

Therapeutic Potential of Targeting ß-Arrestin

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