Restoration of Arpin suppresses aggressive phenotype of breast cancer cells

Li, Yi; Qiu, Jiliang; Pang, Ting; Guo, Zhixing; Su, Yonghui; Zeng, Quan; Zhang, Xuexia

doi:10.1016/j.biopha.2017.05.053

Cited by 11 publications

(6 citation statements)

References 24 publications

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“…Consistently, ARPIN downregulation in breast cancer and its association with a poor prognosis has been reported ( Lomakina et al, 2016 ). Moreover, the restoration of ARPIN in breast cancer cells was shown to suppress the cancer’s aggressiveness ( Li et al, 2017 ). Thus, the regulation of Arp2/3 via ARPIN seems to play a key role in the metastatic conversion of cancer cells.…”

Section: Introductionmentioning

confidence: 99%

RNA Editing Enzyme ADAR1 Suppresses the Mobility of Cancer Cells via ARPIN

Park

Jeong

Lee

et al. 2023

Molecules and Cells

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Deamination of adenine or cytosine in RNA, called RNA editing, is a constitutively active and common modification. The primary role of RNA editing is tagging RNA right after its synthesis so that the endogenous RNA is recognized as self and distinguished from exogenous RNA, such as viral RNA. In addition to this primary function, the direct or indirect effects on gene expression can be utilized in cancer where a high level of RNA editing activity persists. This report identified actin-related protein 2/3 complex inhibitor (ARPIN) as a target of ADAR1 in breast cancer cells. Our comparative RNA sequencing analysis in MCF7 cells revealed that the expression of ARPIN was decreased upon ADAR1 depletion with altered editing on its 3'UTR. However, the expression changes of ARPIN were not dependent on 3'UTR editing but relied on three microRNAs acting on ARPIN. As a result, we found that the migration and invasion of cancer cells were profoundly increased by ADAR1 depletion, and this cellular phenotype was reversed by the exogenous ARPIN expression. Altogether, our data suggest that ADAR1 suppresses breast cancer cell mobility via the upregulation of ARPIN.

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Section: Introductionmentioning

confidence: 99%

RNA Editing Enzyme ADAR1 Suppresses the Mobility of Cancer Cells via ARPIN

Park

Jeong

Lee

et al. 2023

Molecules and Cells

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“…In particular, UC increases the risk to develop colorectal cancer ( Rabbenou and Ullman, 2020 ). Arpin downregulation has been associated with the development of different cancer types, including colon cancer ( Lomakina et al, 2016 ; Li T. et al, 2017 ; Li Y. et al, 2017 ; Zhang et al, 2018 ). Thus, a treatment that restores arpin expression, as shown here for mesalazine, is critical not only for UC treatment but also for colon cancer prevention.…”

Section: Discussionmentioning

confidence: 99%

“…The most recently identified PIA is arpin that competes with the WAVE complex in lamellipodia to regulate random cell migration ( Dang et al, 2013 ), but not chemotaxis ( Dang et al, 2017 ). While the importance of arpin has been shown in different cancer types ( Liu et al, 2016 ; Lomakina et al, 2016 ; Li T. et al, 2017 ; Li Y. et al, 2017 ; Zhang et al, 2019 ), nothing is known about arpin functions in intestinal epithelium and in epithelial barrier regulation during inflammatory disorders including UC.…”

Section: Introductionmentioning

confidence: 99%

The Arp2/3 Inhibitory Protein Arpin Is Required for Intestinal Epithelial Barrier Integrity

Chánez-Paredes

Montoya-García

Castro-Ochoa

et al. 2021

Front. Cell Dev. Biol.

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The intestinal epithelial barrier (IEB) depends on stable interepithelial protein complexes such as tight junctions (TJ), adherens junctions (AJ), and the actin cytoskeleton. During inflammation, the IEB is compromised due to TJ protein internalization and actin remodeling. An important actin regulator is the actin-related protein 2/3 (Arp2/3) complex, which induces actin branching. Activation of Arp2/3 by nucleation-promoting factors is required for the formation of epithelial monolayers, but little is known about the relevance of Arp2/3 inhibition and endogenous Arp2/3 inhibitory proteins for IEB regulation. We found that the recently identified Arp2/3 inhibitory protein arpin was strongly expressed in intestinal epithelial cells. Arpin expression decreased in response to tumor necrosis factor (TNF)α and interferon (IFN)γ treatment, whereas the expression of gadkin and protein interacting with protein C-kinase α-subunit 1 (PICK1), other Arp2/3 inhibitors, remained unchanged. Of note, arpin coprecipitated with the TJ proteins occludin and claudin-1 and the AJ protein E-cadherin. Arpin depletion altered the architecture of both AJ and TJ, increased actin filament content and actomyosin contractility, and significantly increased epithelial permeability, demonstrating that arpin is indeed required for maintaining IEB integrity. During experimental colitis in mice, arpin expression was also decreased. Analyzing colon tissues from ulcerative colitis patients by Western blot, we found different arpin levels with overall no significant changes. However, in acutely inflamed areas, arpin was significantly reduced compared to non-inflamed areas. Importantly, patients receiving mesalazine had significantly higher arpin levels than untreated patients. As arpin depletion (theoretically meaning more active Arp2/3) increased permeability, we wanted to know whether Arp2/3 inhibition would show the opposite. Indeed, the specific Arp2/3 inhibitor CK666 ameliorated TNFα/IFNγ-induced permeability in established Caco-2 monolayers by preventing TJ disruption. CK666 treatment also attenuated colitis development, colon tissue damage, TJ disruption, and permeability in dextran sulphate sodium (DSS)-treated mice. Our results demonstrate that loss of arpin triggers IEB dysfunction during inflammation and that low arpin levels can be considered a novel hallmark of acute inflammation.

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“…However, later studies demonstrated that arpin did not regulate chemotaxis (Dang et al 2017 ). Subsequently, arpin has been studied in different cancer types (Lomakina et al 2016 ;Li, Zheng, et al 2017;, where its downregulation correlated with poor prognosis of the disease and high migratory capability and invasiveness of the tumor cells (Li, Qiu, et al 2017;Lomakina et al 2016 ). We have shown that arpin was expressed in colon epithelial cells and that patients with ulcerative colitis had lower levels of arpin in acutely inflamed tissue areas.…”

Section: Introductionmentioning

confidence: 99%

Arpin deficiency increases actomyosin contractility and vascular permeability

Montoya-Garcia,

Guerrero-Fonseca,

Chanez-Paredes

et al. 2024

eLife

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Arpin was discovered as an inhibitor of the Arp2/3 complex localized at the lamellipodial tip of fibroblasts, where it regulated migration steering. Recently, we showed that arpin stabilizes the epithelial barrier in an Arp2/3-dependent manner. However, expression and functions of arpin in endothelial cells (EC) have not yet been described. Arpin mRNA and protein are expressed in EC and downregulated by pro-inflammatory cytokines. Arpin depletion in HUVEC causes the formation of actomyosin stress fibers leading to increased permeability in an Arp2/3-independent manner. Instead, inhibitors of ROCK1 and ZIPK, kinases involved in the generation of stress fibers, normalize the loss-of-arpin effects on actin filaments and permeability. Arpin-deficient mice are viable but show a characteristic vascular phenotype in the lung including edema, microhemorrhage and vascular congestion, increased F-actin levels and vascular permeability. Our data show that, apart from being an Arp2/3 inhibitor, arpin is also a regulator of actomyosin contractility and endothelial barrier integrity.

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Restoration of Arpin suppresses aggressive phenotype of breast cancer cells

Cited by 11 publications

References 24 publications

RNA Editing Enzyme ADAR1 Suppresses the Mobility of Cancer Cells via ARPIN

RNA Editing Enzyme ADAR1 Suppresses the Mobility of Cancer Cells via ARPIN

The Arp2/3 Inhibitory Protein Arpin Is Required for Intestinal Epithelial Barrier Integrity

Arpin deficiency increases actomyosin contractility and vascular permeability

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