Vimentin Intermediate Filaments as Potential Target for Cancer Treatment

Strouhalova, Katerina; Přechová, Magdalena; Gandalovičová, Aneta; Brábek, Jan; Gregor, Martin; Rösel, Daniel

doi:10.3390/cancers12010184

Cited by 188 publications

(161 citation statements)

References 134 publications

(191 reference statements)

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“…Table 1 summarizes some of the strategies and active principles employed to target vimentin, or reported to affect its function, some of which will be discussed below. In addition, several recent reviews have considered the role of vimentin as a drug target [10,166].…”

Section: Strategies To Modulate Vimentin Function: Focus On Extracellmentioning

confidence: 99%

Vimentin as a Multifaceted Player and Potential Therapeutic Target in Viral Infections

Ramos

Stamatakis

Oeste

et al. 2020

IJMS

140

121

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Vimentin is an intermediate filament protein that plays key roles in integration of cytoskeletal functions, and therefore in basic cellular processes such as cell division and migration. Consequently, vimentin has complex implications in pathophysiology. Vimentin is required for a proper immune response, but it can also act as an autoantigen in autoimmune diseases or as a damage signal. Although vimentin is a predominantly cytoplasmic protein, it can also appear at extracellular locations, either in a secreted form or at the surface of numerous cell types, often in relation to cell activation, inflammation, injury or senescence. Cell surface targeting of vimentin appears to associate with the occurrence of certain posttranslational modifications, such as phosphorylation and/or oxidative damage. At the cell surface, vimentin can act as a receptor for bacterial and viral pathogens. Indeed, vimentin has been shown to play important roles in virus attachment and entry of severe acute respiratory syndrome-related coronavirus (SARS-CoV), dengue and encephalitis viruses, among others. Moreover, the presence of vimentin in specific virus-targeted cells and its induction by proinflammatory cytokines and tissue damage contribute to its implication in viral infection. Here, we recapitulate some of the pathophysiological implications of vimentin, including the involvement of cell surface vimentin in interaction with pathogens, with a special focus on its role as a cellular receptor or co-receptor for viruses. In addition, we provide a perspective on approaches to target vimentin, including antibodies or chemical agents that could modulate these interactions to potentially interfere with viral pathogenesis, which could be useful when multi-target antiviral strategies are needed.

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Section: Strategies To Modulate Vimentin Function: Focus On Extracellmentioning

confidence: 99%

Vimentin as a Multifaceted Player and Potential Therapeutic Target in Viral Infections

Ramos

Stamatakis

Oeste

et al. 2020

IJMS

140

121

View full text Add to dashboard Cite

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“…Our findings indicated that the levels of SMAD-2, SMAD-3, and their phosphorylated forms decreased in a dose-dependent way following APE treatment. Then, we analyzed vimentin, a type III intermediate filament and a major cytoskeletal component of motile mesenchymal cells, including metastatic tumor cells of epithelial origin 25 . Western blot analyses confirmed that MDA-MB-231 cells express high levels of vimentin which, after 48 h treatment with APE 300 μM EqC, became only slightly detectable suggesting APE-induced modifications of mesenchymal cell phenotype.…”

Section: Ape Decreased Mesenchymal and Increased Epithelial Markers Ementioning

confidence: 99%

“…Vimentin is overexpressed in most epithelial cancers and its levels correlate with tumor migration, invasion, and poor prognosis. Drugs inhibiting or reversing EMT also affect vimentin network organization 25 . Vimentin plays an important role in the formation of lamellipodia and filopodia 27 , specialized actin-rich plasma membrane protrusions with proteolytic activity, that allow cancer cells to degrade ECM with directional movement enabling cell invasion 28 .…”

Section: Ape Induced Met In Mda-mb-231 Cells By Modifying Vimentin Exmentioning

confidence: 99%

Annurca apple polyphenol extract promotes mesenchymal-to-epithelial transition and inhibits migration in triple-negative breast cancer cells through ROS/JNK signaling

Vuoso

D’Angelo

Ferraro

et al. 2020

Sci Rep

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Aberrant activation of epithelial-to-mesenchymal transition has been shown to correlate with triple-negative breast cancer (TNBC) progression and metastasis. Thus, the induction of the reverse process might offer promising opportunities to restrain TNBC metastatic spreading and related mortality. Recently, the Annurca apple polyphenol extract (APE) has been highlighted as a multi-faceted agent that selectively kills TNBC cells by ROS generation and sustained JNK activation. Here, by qualitatively and quantitatively monitoring the real-time movements of live cells we provided the first evidence that APE inhibited the migration of MDA-MB-231 and MDA-MB-468 TNBC cells and downregulated metalloproteinase-2 and metalloproteinase-9. In MDA-MB-231 cells APE decreased SMAD-2/3 and p-SMAD-2/3 levels, increased E-cadherin/N-cadherin protein ratio, induced the switch from N-cadherin to E-cadherin expression and greatly reduced vimentin levels. Confocal and scanning electron microscopy imaging of APE-treated MDA-MB-231 cells evidenced a significant cytoskeletal vimentin and filamentous actin reorganization and revealed considerable changes in cell morphology highlighting an evident transition from the mesenchymal to epithelial phenotype with decreased migratory features. Notably, all these events were reverted by N-acetyl-l-cysteine and JNK inhibitor SP600125 furnishing evidence that APE exerted its effects through the activation of ROS/JNK signaling. The overall data highlighted APE as a potential preventing agent for TNBC metastasis.

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“…Among several pathways that induce EMT, a downregulation of epithelial protein, E-cadherin and a gain of the mesenchymal protein Vimentin have been found to play a critical role in cancer progression and metastasis [75,76]. Therefore, the tight regulation of these two functional opposite proteins is mandatory for cancer cells to control their aggressiveness and treatment responsiveness.…”

Section: Ubqlns and Emt Markersmentioning

confidence: 99%

Ubiquilin Networking in Cancers

Jantrapirom

Piccolo

Pruksakorn

et al. 2020

Cancers

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Ubiquilins or UBQLNs, members of the ubiquitin-like and ubiquitin-associated domain (UBL-UBA) protein family, serve as adaptors to coordinate the degradation of specific substrates via both proteasome and autophagy pathways. The UBQLN substrates reveal great diversity and impact a wide range of cellular functions. For decades, researchers have been attempting to uncover a puzzle and understand the role of UBQLNs in human cancers, particularly in the modulation of oncogene’s stability and nucleotide excision repair. In this review, we summarize the UBQLNs’ genetic variants that are associated with the most common cancers and also discuss their reliability as a prognostic marker. Moreover, we provide an overview of the UBQLNs networks that are relevant to cancers in different ways, including cell cycle, apoptosis, epithelial-mesenchymal transition, DNA repairs and miRNAs. Finally, we include a future prospective on novel ubiquilin-based cancer therapies.

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Vimentin Intermediate Filaments as Potential Target for Cancer Treatment

Cited by 188 publications

References 134 publications

Vimentin as a Multifaceted Player and Potential Therapeutic Target in Viral Infections

Vimentin as a Multifaceted Player and Potential Therapeutic Target in Viral Infections

Annurca apple polyphenol extract promotes mesenchymal-to-epithelial transition and inhibits migration in triple-negative breast cancer cells through ROS/JNK signaling

Ubiquilin Networking in Cancers

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