Focal adhesion-mediated cell anchoring and migration: from<i>in vitro</i>to<i>in vivo</i>

Yamaguchi, Naoya; Knaut, Holger

doi:10.1242/dev.200647

Cited by 27 publications

(8 citation statements)

References 295 publications

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“…The anticancer adjuvant (SBsib-711) targets the molecular players of cell adhesion and migration, which are critical for cancer metastasis, such as focal adhesion (FA) and extracellular matrix (ECM) receptors ( Figure 11 c). FAs are protein complexes attaching cells to the ECM cytoskeleton, providing actin–integrin links [ 44 ]. Anticancer peptides affect cell-adhesion molecules (CAMs) to prevent tumor metastasis [ 45 ].…”

Section: Resultsmentioning

confidence: 99%

Immunomodulatory Peptides as Vaccine Adjuvants and Antimicrobial Agents

Hemmati,

Saeidikia,

Seradj

et al. 2024

Pharmaceuticals

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The underdevelopment of adjuvant discovery and diversity, compared to core vaccine technology, is evident. On the other hand, antibiotic resistance is on the list of the top ten threats to global health. Immunomodulatory peptides that target a pathogen and modulate the immune system simultaneously are promising for the development of preventive and therapeutic molecules. Since investigating innate immunity in insects has led to prominent achievements in human immunology, such as toll-like receptor (TLR) discovery, we used the capacity of the immunomodulatory peptides of arthropods with concomitant antimicrobial or antitumor activity. An SVM-based machine learning classifier identified short immunomodulatory sequences encrypted in 643 antimicrobial peptides from 55 foe-to-friend arthropods. The critical features involved in efficacy and safety were calculated. Finally, 76 safe immunomodulators were identified. Then, molecular docking and simulation studies defined the target of the most optimal peptide ligands among all human cell-surface TLRs. SPalf2-453 from a crab is a cell-penetrating immunoadjuvant with antiviral properties. The peptide interacts with the TLR1/2 heterodimer. SBsib-711 from a blackfly is a TLR4/MD2 ligand used as a cancer vaccine immunoadjuvant. In addition, SBsib-711 binds CD47 and PD-L1 on tumor cells, which is applicable in cancer immunotherapy as a checkpoint inhibitor. MRh4-679 from a shrimp is a broad-spectrum or universal immunoadjuvant with a putative Th1/Th2-balanced response. We also implemented a pathway enrichment analysis to define fingerprints or immunological signatures for further in vitro and in vivo immunogenicity and reactogenicity measurements. Conclusively, combinatorial machine learning, molecular docking, and simulation studies, as well as systems biology, open a new opportunity for the discovery and development of multifunctional prophylactic and therapeutic lead peptides.

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Section: Resultsmentioning

confidence: 99%

Immunomodulatory Peptides as Vaccine Adjuvants and Antimicrobial Agents

Hemmati,

Saeidikia,

Seradj

et al. 2024

Pharmaceuticals

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“…Complementary to the prior studies in which bisulfite sequencing was utilized, the most common motif “AGSCDGG” was identified by m5C-antibody based m5C-seq. KEGG analysis showed that differentially methylated sites-harboring genes were mainly enriched in several oncogenic pathways, which are closely related with tumor growth and metastasis [ 36 , 37 ]. Subsequently, we identified TIAM2 as a downstream target of NSUN2 by sequencing and bioinformatics analysis.…”

Section: Discussionmentioning

confidence: 99%

NSUN2 stimulates tumor progression via enhancing TIAM2 mRNA stability in pancreatic cancer

Zhang

Liu

et al. 2023

Cell Death Discov.

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NSUN2 is a nuclear RNA methyltransferase which catalyzes 5-methylcytosine (m5C), a posttranscriptional RNA modification. Aberrant m5C modification has been implicated in the development of multiple malignancies. However, its function in pancreatic cancer (PC) needs to be elucidated. Herein, we determined that NSUN2 was overexpressed in PC tissues and related to aggressive clinical features. Silence of NSUN2 by lentivirus weakened the capability of proliferation, migration and invasion of PC cells in vitro and inhibited the growth and metastasis of xenograft tumors in vivo. Contrarily, overexpression of NSUN2 stimulated PC growth and metastasis. Mechanistically, m5C-sequencing (m5C-seq) and RNA-sequencing (RNA-seq) were carried out to identify downstream targets of NSUN2 and results showed that loss of NSUN2 led to decreased m5C modification level concomitant with reduced TIAM2 mRNA expression. Further validation experiments proved that NSUN2 silence accelerated the decay of TIAM2 mRNA in a YBX1-dependent manner. Additionally, NSUN2 exerted its oncogenic function partially through enhancing TIAM2 transcription. More importantly, disruption of the NSUN2/TIAM2 axis repressed the malignant phenotype of PC cells through blocking epithelial-mesenchymal transition (EMT). Collectively, our study highlighted the critical function of NSUN2 in PC and provided novel mechanistic insights into NSUN2/TIAM2 axis as promising therapeutic targets against PC.

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“…Focal-adhesion-based cell–extracellular matrix interactions are essential for cell anchoring and cell migration, and plays a crucial role in development, immunity, and disease [ 53 , 54 , 55 ]. Research has revealed that herpes simplex virus 1 (HSV–1) envelop proteins (pUL7 and pUL51), localize to focal adhesions on the cytoplasmic membrane, and maintain the attachment of infected cells to their surrounding environment by modulating the activity of focal adhesion complexes [ 56 ].…”

Section: Discussionmentioning

confidence: 99%

Altered Proteomic Profile of Exosomes Secreted from Vero Cells Infected with Porcine Epidemic Diarrhea Virus

Shen

et al. 2023

Viruses

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Porcine epidemic diarrhea virus (PEDV) infection causes severe diarrhea in pigs and can be fatal in newborn piglets. Exosomes are extracellular vesicles secreted by cells that transfer biologically active proteins, lipids, and RNA to neighboring or distant cells. Herein, the morphology, particle size, and secretion of exosomes derived from a control and PEDV-infected group are examined, followed by a proteomic analysis of the exosomes. The results show that the exosomes secreted from the Vero cells had a typical cup–shaped structure. The average particle size of the exosomes from the PEDV-infected group was 112.4 nm, whereas that from the control group was 150.8 nm. The exosome density analysis and characteristic protein determination revealed that the content of exosomes in the PEDV-infected group was significantly higher than that in the control group. The quantitative proteomics assays revealed 544 differentially expressed proteins (DEPs) in the PEDV-infected group’s exosomes compared with those in the controls, with 236 upregulated and 308 downregulated proteins. The DEPs were closely associated with cellular regulatory pathways, such as the phosphatidylinositol–4,5–bisphosphate 3–kinase (PI3K)–protein kinase B (Akt) signaling pathway, extracellular matrix–receptor interaction, focal adhesion, and cytoskeletal regulation. These findings provide the basis for further investigation of the pathogenic mechanisms of PEDV and the discovery of novel antiviral targets.

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Focal adhesion-mediated cell anchoring and migration: fromin vitrotoin vivo

Cited by 27 publications

References 295 publications

Immunomodulatory Peptides as Vaccine Adjuvants and Antimicrobial Agents

Immunomodulatory Peptides as Vaccine Adjuvants and Antimicrobial Agents

NSUN2 stimulates tumor progression via enhancing TIAM2 mRNA stability in pancreatic cancer

Altered Proteomic Profile of Exosomes Secreted from Vero Cells Infected with Porcine Epidemic Diarrhea Virus

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