PRP4 kinase induces actin rearrangement and epithelial-mesenchymal transition through modulation of the actin-binding protein cofilin

Islam, Salman Ul; Ahmed, Muhammad Bilal; Lee, Su Jin; Shehzad, Adeeb; Sonn, Jong Kyung; Kwon, Oh Nam; Lee, Young-Sup

doi:10.1016/j.yexcr.2018.05.018

Cited by 19 publications

(13 citation statements)

References 44 publications

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“…Numerous signaling pathways control the rearrangement of actin cytoskeleton, such as Rho family of GTPases and kinases. For example, RhoA activates Rho kinase (ROCK), which then increases myosin light chain and LIM-kinase phosphorylation and inhibits myosin light chain phosphatase, resulting in the facilitation of actinomyosin assembly, and inhibition of cofilin, an actin depolymerizing protein 42 , 43 . This stabilizes the actin and helps cells and neurons maintain a strong cyto-architecture.…”

Section: Discussionmentioning

confidence: 99%

Protein-protein interactions reveal key canonical pathways, upstream regulators, interactome domains, and novel targets in ALS

Dervishi

Gozutok

Murnan

et al. 2018

Sci Rep

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Developing effective treatment strategies for neurodegenerative diseases require an understanding of the underlying cellular pathways that lead to neuronal vulnerability and progressive degeneration. To date, numerous mutations in 147 distinct genes are identified to be “associated” with, “modifier” or “causative” of amyotrophic lateral sclerosis (ALS). Protein products of these genes and their interactions helped determine the protein landscape of ALS, and revealed upstream modulators, key canonical pathways, interactome domains and novel therapeutic targets. Our analysis originates from known human mutations and circles back to human, revealing increased PPARG and PPARGC1A expression in the Betz cells of sALS patients and patients with TDP43 pathology, and emphasizes the importance of lipid homeostasis. Downregulation of YWHAZ, a 14-3-3 protein, and cytoplasmic accumulation of ZFYVE27 especially in diseased Betz cells of ALS patients reinforce the idea that perturbed protein communications, interactome defects, and altered converging pathways will reveal novel therapeutic targets in ALS.

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Section: Discussionmentioning

confidence: 99%

Protein-protein interactions reveal key canonical pathways, upstream regulators, interactome domains, and novel targets in ALS

Dervishi

Gozutok

Murnan

et al. 2018

Sci Rep

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“…However, PRP8 remained unaffected (Figure 2(b)). Previously, it has been shown that PRP4 altered cell morphology in cancer cell lines (Islam et al 2017;Islam, Ahmed et al 2018). In order analyze the correlation of LPS with PRP4 regarding cell cytoskeleton rearrangement, cells were pre-treated with LPS and transiently transfected with a PRP4 expression construct.…”

Section: Resultsmentioning

confidence: 99%

“…Previously, it has been reported that PRP4 is involved in reversing anticancer drug-induced cell death in human cancer cell lines through actin cytoskeleton rearrangement and epithelial-mesenchymal transition (EMT) (Islam et al 2017;Islam, Ahmed, et al 2018). Herein, we report that LPS induced the activation of PRP4 which resulted in the activation of various cytokines and inflammatory proteins.…”

Section: Introductionmentioning

confidence: 86%

“…Total RNA (5 µg) was reverse-transcribed using the SuperScript III First-strand synthesis kit, as has been described previously (Islam et al 2015;Islam, Ahmed et al 2018). The synthesized cDNA was incubated with RNase H at 37°C for 1 h. PCR was performed using 2 μL of cDNA and the following primers: following primers: IL-6 Forward 5 ′ -GGTACATCCTCGACGGCATCT-3 ′ and Reverse 5 ′ -GTGCCTCTTTGCTGCTTTCAC-3 ′ and IL-1β Forward 5 ′ -ACAGATGAAGTGCTCCTTCCA-3 ′ and Reverse 5 ′ -GTCGGAGATTCGTAGCTGGAT-3 ′ and glyceraldehyde-3-phosphate dehydrogenase (GAPDH) forward, 5ʹ-AGGGCTGCTTTTAACTCTGGT-3ʹ and GAPDH reverse, 5ʹ-CCCCACTTGATTTTGGAGGGA-3ʹ.…”

Section: Reverse-transcription Polymerase Chain Reaction (Rt-pcr)mentioning

confidence: 99%

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Decursin negatively regulates LPS-induced upregulation of the TLR4 and JNK signaling stimulated by the expression of PRP4in vitro

Ahmed

Islam

Lee

2020

Animal Cells and Systems

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The current investigation was carried out to analyze the correlation of bacterial lipopolysaccharide (LPS) and pre-mRNA processing factor 4B (PRP4) in inducing inflammatory response and cell actin cytoskeleton rearrangement in macrophages (Raw 264.7) and colorectal (HCT116) as well as skin cancer (B16-F10) cells. Cell lines were stimulated with LPS, and the expression of PRP4 as well as pro-inflammatory cytokines and proteins like IL-6, IL-1β, TLR4, and NF-κB were assayed. The results demonstrated that LPS markedly increased the expression of PRP4, IL-6, IL-1β, TLR4, and NF-κB in the cells. LPS and PRP4 concomitantly altered the morphology of cells from an aggregated, flattened shape to a round shape. Decursin, a pyranocoumarin from Angelica gigas, inhibited the LPS and PRP4-induced inflammatory response, and reversed the induction of morphological changes. Finally, we established a possible link of LPS with TLR4 and JNK signaling, through which it activated PRP4. Our study provides molecular insights for LPS and PRP4-related pathogenesis and a basis for developing new strategies against metastasis in colorectal cancer and skin melanoma. Our study emphasizes that decursin may be an effective treatment strategy for various cancers in which LPS and PRP4 perform a critical role in inducing inflammatory response and morphological changes leading to cell survival and protection against anti-cancer drugs. ARTICLE HISTORY

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“…The membranes were blocked with 3% albumin (Gendepot, USA) solution for 2 h at 4°C. Chemiluminescent signals were developed using Clarity™ ECL Western Blotting Substrate (Bio-Rad) according to the manufacturer's instructions [18, 24].…”

Section: Methodsmentioning

confidence: 99%

Methanolic Extract ofArtemia salinaEggs and Various Fractions in Different Solvents Contain Potent Compounds That Decrease Cell Viability of Colon and Skin Cancer Cell Lines and Show Antibacterial Activity againstPseudomonas aeruginosa

Islam

Ahmed

Shehzad

et al. 2019

Evidence-Based Complementary and Alternative Medicine

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Artemia salina, crustaceans of class Branchiopoda and order Anostraca, are living and reproducing only in highly saline natural lakes and in other reservoirs where sea water is evaporated to produce salt. Artemia salina eggs can be purchased from pet stores, where they are sold as tropical fish food and a ready source for hatching shrimp. In the current study, methanolic crude extracts and various fractions of Artemia salina eggs extracted in other solvents were tested for effects on cell viability of human colorectal cancer cells (HCT116) and melanoma cells (B16F10) using an MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) assay. A methanolic crude extract of eggs was obtained by cold maceration, followed by fractionation to obtain hexane, chloroform, ethyl acetate, n-butanol, and aqueous fractions. The methanolic crude extract decreased cell viability of HCT-116 and B16F10 cell lines at higher concentrations. The other fractions were evaluated using a cell viability assay, and chloroform and hexane showed the highest activity at significantly lower concentrations than did the methanolic fraction. Full scan profiles of the methanolic crude extract and the chloroform and hexane fractions were obtained by gas chromatography mass spectrometry (GC-MS), and the resultant compounds were identified by comparing their spectral data to those available in spectral matching libraries. ROS generation assay, flow cytometry, and western blot analysis provided supporting evidence that the hexane and chloroform fractions induced cell death in HCT116 and B16-F10 cell lines. All fractions were further tested for antibacterial activity against Pseudomonas aeruginosa, among which the hexane fraction showed the highest zone of inhibition on LB nutrient agar plates. This study demonstrated promising anticancer and antibacterial effects of Artemia salina egg extracts. Our results suggest that pure bioactive compounds obtained from Artemia salina eggs can provide new insights into the mechanisms of colon and skin cancer, as well as Pseudomonas aeruginosa inhibition.

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PRP4 kinase induces actin rearrangement and epithelial-mesenchymal transition through modulation of the actin-binding protein cofilin

Cited by 19 publications

References 44 publications

Protein-protein interactions reveal key canonical pathways, upstream regulators, interactome domains, and novel targets in ALS

Protein-protein interactions reveal key canonical pathways, upstream regulators, interactome domains, and novel targets in ALS

Decursin negatively regulates LPS-induced upregulation of the TLR4 and JNK signaling stimulated by the expression of PRP4in vitro

Methanolic Extract ofArtemia salinaEggs and Various Fractions in Different Solvents Contain Potent Compounds That Decrease Cell Viability of Colon and Skin Cancer Cell Lines and Show Antibacterial Activity againstPseudomonas aeruginosa

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