Cell Adhesion Signaling Research Articles

The impact of glucocorticoid receptor transactivation on context-dependent cell migration dynamics

The glucocorticoid receptor (GR) plays a significant role in breast cancer cell behaviour, although data on its effects are conflicting. The impact of GR agonist dexamethasone (dex) and antagonist mifepristone (mif) on oestrogen-positive (ER+) and triple-negative (TN) breast cancer cell lines in both 2D and 3D cultures was studied using multiple in vitro functional assays and transcriptome sequencing. GR activation increased cell motility in TN but not in ER + tumour cells, as observed in both collective and single-cell migration tests. Time-lapse analysis showed enhanced motility after 4–6 h in wound healing, despite dex inhibiting migration initially. This inhibition was observed at 2 h in single-cell tracking migration assays. Cell proliferation increased in TN and decreased in ER + cells upon GR activation, reversed by GR antagonist. RNA sequencing revealed dex’s impact on cell adhesion and extracellular matrix signalling in TN cells and on DNA replication in ER + cells. Based on data from 1085 human breast cancer specimens, GR pathway expression correlated with migratory, extracellular matrix, and angiogenesis gene signatures. Additionally, higher expression of GR and increased GR signature were observed in fast-migrating cells compared to slow-migrating ones. Positive correlation between the GR signature and migration signature at the single-cell level indicated an association between GR activity and cell migration. For the first time, we assessed altered time-lapse migration dynamics in TN breast cancer cells, potentially contributing to cancer progression and prognosis, highlighting that the effects of dexamethasone on breast cancer cell migration are influenced by ER status and treatment duration.

Deciphering the molecular drivers for cashmere/pashmina fiber production in goats: a comprehensive review.

Cashmere, also known as pashmina, is derived from the secondary hair follicles of Cashmere/Changthangi goats. Renowned as the world's most luxurious natural fiber, it holds significant economic value in the textile industry. This comprehensive review enhances our understanding of the complex biological processes governing cashmere/pashmina fiber development and quality, enabling advancements in selective breeding and fiber enhancement strategies. The review specifically examines the molecular determinants influencing fiber development, with an emphasis on keratins (KRTs) and keratin-associated proteins (KRTAPs). It also explores the roles of key molecular pathways, including Wnt, Notch, BMP, NF-kappa B, VEGF, cAMP, PI3K-Akt, ECM, cell adhesion, Hedgehog, MAPK, Ras, JAK-STAT, TGF-β, mTOR, melanogenesis, FoxO, Hippo, and Rap1 signaling. Understanding these intricate molecular cascades provides valuable insights into the mechanisms orchestrating hair follicle growth, further advancing the biology of this coveted natural fiber. Expanding multi-omics approaches will enhance breeding precision and deepen our understanding of molecular pathways influencing cashmere production. Future research should address critical gaps, such as the impact of environmental factors, epigenetic modifications, and functional studies of genetic variants. Collaboration among breeders, researchers, and policymakers is essential for translating genomic advancements into practical applications. Such efforts can promote sustainable practices, conserve biodiversity, and ensure the long-term viability of high-quality cashmere production. Aligning genetic insights with conservation strategies will support the sustainable growth of the cashmere industry while preserving its economic and ecological value.

Comparative transcriptomic analysis of primary endometrial cancer and bone metastatic cancer: metastasis-associated genes and abnormal cell cycle regulation

Endometrial cancer (EC) is the most common tumor of the female reproductive system. Its incidence is rising worldwide. Bone metastasis (BMs) in EC is rarely reported, and is seen in only 0.8% of patients. Once bone metastasis develops, it often indicates a poor prognosis. Current research on the bone metastasis of primary tumors suggests that tumor cells primarily colonize bones through hematogenous metastasis and are stimulated to grow by the bone microenvironment. However, the biological mechanism of bone metastasis in EC remains unclear. In this study, we aim to determine the changes in gene expression profiles in EC bone metastasis and explore the transcriptomic differences between metastatic and primary lesions. We collected one primary EC case and two bone metastasis tumors for transcriptomic analysis. The analysis revealed that numerous genes are involved in regulating the cell cycle and proliferation. Analysis of differentially expressed genes (DEGs) revealed that these genes are involved in the regulation of post-translational modification, protein turnover, and signal transduction mechanisms. E2F1, MCM2, RFC2, and ICAM1 are involved in the metastasis and progression of EC with bone metastasis (ECBM). The Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis indicates significant changes in the Hippo signaling pathway, which regulates cell proliferation, and in the cell adhesion signaling pathway. Numerous transcription factors, including SOX2, NUSAP1, and ACTA1, which promote tumor development, are involved in regulating the expression of cell cycle control genes. Survival curve analysis of high-expression cell cycle genes, including P27, P19, and CDK1, in ECBM showed that elevated levels of these genes are associated with poorer patient survival. Our research identified genes and key signaling pathways associated with bone metastasis. These findings provide a theoretical basis for the treatment of bone metastasis in EC.

Comprehensive pan-cancer analysis reveals NTN1 as an immune infiltrate risk factor and its potential prognostic value in SKCM

Netrin-1 (NTN1) is a laminin-related secreted protein involved in axon guidance and cell migration. Previous research has established a significant connection between NTN1 and nervous system development. In recent years, mounting evidence indicates that NTN1 also plays a crucial role in tumorigenesis and tumor progression. For instance, inhibiting Netrin-1 has been shown to suppress tumor growth and epithelial-mesenchymal transition (EMT) characteristics in endometrial cancer. To further elucidate the influence of genes on tumors, we utilized a variety of machine learning techniques and found that NTN1 is strongly linked to multiple cancer types, suggesting it as a potential therapeutic target. This study aimed to elucidate the role of NTN1 in pan-cancer using multi-omics data and explore its potential as a prognostic biomarker in SKCM. Analysis of the TCGA, GTEx, and UALCAN databases revealed significant differences in NTN1 expression at both the mRNA and protein levels. Prognostic value was evaluated through univariate Cox regression and Kaplan–Meier methods. Mutation and methylation analyses were conducted using the cBioPortal and SMART databases. We identified genes interacting with and correlated to NTN1 through STRING and GEPIA2, respectively. Subsequently, we performed GO and KEGG enrichment analyses. The results suggested that NTN1 might be involved in crucial biological processes and pathways related to cancer development and progression, including cell adhesion, axon guidance, immune response, and various signaling pathways. We then explored the correlation between NTN1 and immune infiltration as well as immunotherapy using the ESTIMATE package, TIMER2.0, TISIDB, TIDE, TIMSO, and TCIA. The relationship between NTN1 and tumor heterogeneity, stemness, DNA methyltransferases, and MMR genes was also examined. Lastly, we constructed a nomogram based on NTN1 in SKCM and investigated its association with drug sensitivity. NTN1 expression was significantly associated with tumor immune infiltration, molecular subtypes, and clinicopathological features in various cancers. Genetic analysis revealed that Deep deletions were the most common type of NTN1 alteration. Additionally, a positive correlation was observed between NTN1 CNAs and its expression levels. In most cancers, NTN1 showed positive correlations with immune and stromal scores, as well as with specific immune cell populations. Its predictive value for immunotherapy response was comparable to that of tumor mutational burden. Furthermore, NTN1 exhibited positive correlations with tumor heterogeneity, stemness, DNA methyltransferase genes, and MMR genes. In SKCM, NTN1 was identified as an independent risk factor and demonstrated potential associations with multiple drugs. NTN1 exhibits substantial clinical utility as a prognostic marker and indicator of immune response across various tumor types. This comprehensive analysis provides insights into its potential implications in pan-cancer research.

The Integrin Receptors: From Discovery to Structure to Medicines.

Innate immune cells perform vital tasks in detecting, seeking, and eliminating invading pathogens, thus ensuring host survival. However, loss of function of these cells or their overactive response to tissue injury often causes serious ailments. It is, therefore, crucial to understand at a basic level how these cells function in health and disease. A major step toward this goal came from studies I conducted in the late 1970s investigating the cause of life-threatening bacterial infections in a pediatric patient. This work led us to trace this disease to the inability of the patient's neutrophils to seek and clear infections due to an inherited deficiency in leukocyte adhesion caused by the loss of a plasma membrane glycoprotein complex now known as CD11/CD18 or β2 integrins. I followed this work by determining the 3-dimensional structures of integrins. These studies provided the foundation for understanding the unique properties of integrins in mediating bidirectional cell adhesion signaling and enabled a structure-guided design of compounds to dial down overactive integrins in common disorders, including thromboinflammatory and autoimmune diseases.

Identification of CSPG4 as a Biomarker and Therapeutic Target for Infantile Post-Hemorrhagic Hydrocephalus via Multi-Omics Analysis.

Intraventricular hemorrhage in preterm neonates has become a major global health problem and is associated with a high risk of post-hemorrhagic hydrocephalus (PHH). Identifying diagnostic markers and therapeutic targets is a focal challenge in the PHH prevention and control. Here, this study applies multi-omics analyses to characterize the biochemical, proteomic, and metabolomic profiles of the cerebrospinal fluid (CSF) in clinical human cohorts to investigate disease development and recovery processes occurring due to PHH. Integrative multiomics analysis suggests that the over-representation of ferroptosis, calcium, calcium ion binding, and cell adhesion signaling pathways is associated with PHH. Bioinformatic analysis indicates that chondroitin sulfate proteoglycan 4 (CSPG4) is discovered as a CSF biomarker and positively correlated with the ventricular size and the rate of periventricular leukomalacia. Next, it is further demonstrated that these signaling pathways are dysregulated in the choroid plexus (ChP) in PHH by using in vitro cellular experiments and rat models of PHH, whereas CSPG4 silencing can suppress ferroptosis, cell adhesion function, and the intracellular flow of Ca2+. These findings broaden the understanding of the pathophysiological mechanisms of PHH and suggest that CSPG4 may be an effective therapeutic target for PHH.

TRIM16 and PRC1 Are Involved in Pancreatic Cancer Progression and Targeted by Delphinidin.

Pancreatic cancer (PC) is the leading cause of cancer-related death worldwide, and new biomarkers, therapeutic targets, and candidate drugs are needed. In this work, three PC-related microarray datasets (GSE183795, GSE28735, and GSE62452) were analyzed. The differentially expressed genes (DEGs) of PC were obtained with the limma package in R. Weighted gene co-expression network analysis (WGCNA) and machine learning approaches were used to screen the hub genes. Kaplan-Meier plotter and receiver operating characteristic (ROC) curve analysis were utilized to assess the diagnostic efficacy of the hub genes. The binding ability between natural bioactive ingredients and hub proteins was evaluated by molecular docking and molecular dynamics simulation. CCK-8, flow cytometry, transwell, and western blot assays were used to analyze the viability, apoptosis, cell cycle progression, invasion, and pathway change of PC cells. Additionally, a nude mice model was used to evaluate the aggressive properties of PC cells invivo. In this study, a total of 988 DEGs were identified, which were mainly enriched in cell adhesion and PI3K-Akt signaling pathway, and two core genes TRIM16 and PRC1 were further identified. The overall survival of patients with high expression of TRIM16 and PRC1 was shorter. Delphinidin (Del) had good binding affinity with both TRIM16 and PRC1, and Del could inhibit the viability, invasion, and metastasis of PC cells and induce cell apoptosis and G0/G1 phase arrest. In addition, Del could promote the activation of p53 and inhibit the activation of the PI3K/AKT signaling pathway in PC cells. In summary, TRIM16 and PRC1 are identified as prognostic biomarkers and therapeutic targets for PC, and Del has good binding affinity with them and may be a potential therapeutic agent for PC.

An organotypic atlas of human vascular cells

The human vascular system, comprising endothelial cells (ECs) and mural cells, covers a vast surface area in the body, providing a critical interface between blood and tissue environments. Functional differences exist across specific vascular beds, but their molecular determinants across tissues remain largely unknown. In this study, we integrated single-cell transcriptomics data from 19 human organs and tissues and defined 42 vascular cell states from approximately 67,000 cells (62 donors), including angiotypic transitional signatures along the arterial endothelial axis from large to small caliber vessels. We also characterized organotypic populations, including splenic littoral and blood–brain barrier ECs, thus clarifying the molecular profiles of these important cell states. Interrogating endothelial–mural cell molecular crosstalk revealed angiotypic and organotypic communication pathways related to Notch, Wnt, retinoic acid, prostaglandin and cell adhesion signaling. Transcription factor network analysis revealed differential regulation of downstream target genes in tissue-specific modules, such as those of FOXF1 across multiple lung vascular subpopulations. Additionally, we make mechanistic inferences of vascular drug targets within different vascular beds. This open-access resource enhances our understanding of angiodiversity and organotypic molecular signatures in human vascular cells, and has therapeutic implications for vascular diseases across tissues.

Recurrent somatic mutations of FAT family cadherins induce an aggressive phenotype and poor prognosis in anaplastic large cell lymphoma

BackgroundAnaplastic Large Cell Lymphoma (ALCL) is a rare and aggressive T-cell lymphoma, classified into ALK-positive and ALK-negative subtypes, based on the presence of chromosomal translocations involving the ALK gene. The current standard of treatment for ALCL is polychemotherapy, with a high overall survival rate. However, a subset of patients does not respond to or develops resistance to these therapies, posing a serious challenge for clinicians. Recent targeted treatments such as ALK kinase inhibitors and anti-CD30 antibody-drug conjugates have shown promise but, for a fraction of patients, the prognosis is still unsatisfactory.MethodsWe investigated the genetic landscape of ALK + ALCL by whole-exome sequencing; recurring mutations were characterized in vitro and in vivo using transduced ALCL cellular models.ResultsRecurrent mutations in FAT family genes and the transcription factor RUNX1T1 were found. These mutations induced changes in ALCL cells morphology, growth, and migration, shedding light on potential factors contributing to treatment resistance. In particular, FAT4 silencing in ALCL cells activated the β-catenin and YAP1 pathways, which play crucial roles in tumor growth, and conferred resistance to chemotherapy. Furthermore, STAT1 and STAT3 were hyper-activated in these cells. Gene expression profiling showed global changes in pathways related to cell adhesion, cytoskeletal organization, and oncogenic signaling. Notably, FAT mutations associated with poor outcome in patients.ConclusionsThese findings provide novel insights into the molecular portrait of ALCL, that could help improve treatment strategies and the prognosis for ALCL patients.

Biomarker Discovery via N-Glycoproteomics.

Posttranslational modifications (PTMs) of proteins regulate several biological processes, and investigating their diversity is crucial for understanding the mechanisms of cell regulation. Glycosylation is one of the most complex posttranslational modifications that control fundamental cellular processes such as protein folding, protein trafficking, host-pathogen interactions, cell adhesion, and cytokine receptor signaling networks. N-linked glycosylation denotes the attachment of glycans (oligosaccharides) to a nitrogen atom of asparagine (N) residues in the consensus motif Asn-X-Ser/Thr (NXS/T), where X is any amino acid except proline. Therefore, mutations in this posttranslational modification (i.e., N-glycosylation) site cause many human genetic diseases, including cancer. In the past decade, high-throughput quantitative proteome profiling tools have significantly renewed our interest in discovering novel cancer diagnostic or prognostic biomarkers through the simultaneous examination of the enormous amount of high-quality data of thousands of proteins and genes in complex biological systems. In this chapter, we describe how aberrant N-linked glycopeptides could be selectively identified as novel single tumor markers through the use of mass spectrometry (MS)-based proteomics, also known as Solid-phase extraction of N-glycopeptides (SPEG), and reasonable hypotheses that have the potential capacity to revolutionize biomarker discovery and bring those markers to the clinic as early as possible.

Focal Adhesion Kinase (FAK) and c-Src Dependent Signal Transduction in Cell Adhesion.

This review predominantly acquaints the role of focal adhesion kinase (FAK) and cellular-Src (c-Src) in cell adhesion. Cell adhesion is a crucial phenomenon that causes the cells to interact with the extracellular matrix (ECM) or with each other. There are different proteins involved in cell adhesion including cell adhesion molecules (CAMs)/receptors that are present on the cell surface and various cytoplasmic proteins. FAK and c-Src are two proteins in the cytoplasm, which serve as regulators of different proteins involved in cell adhesion. They activate talin, vinculin and paxillin in turn connect the integrins with the cytoskeleton and in this way strengthen the integrin interaction with ECM. FAK-Src signalling also modulates cell-cell adhesion by regulating actin interactions. Being a key modulator of cell adhesion, FAK and c-Src signalling are linked with different pathological conditions like cancer, cardiovascular diseases, and embryonic developmental disorders. Thus, comprehensive research into FAK-Src signalling is of great importance in the exploration of different signalling targets for therapeutic interpretations. Different inhibitors and antibodies against various cell adhesion proteins, such as FAK, c-Src, and integrins, have already been used in preclinical and clinical trials to treat a variety of diseases, including cancer and chronic inflammatory conditions. Furthermore, this review presents different challenges to FAK-Src and cell adhesion signalling targeted drug development, which include, cytotoxicity and cell resistance to the drug. Finally, this review remarks that FAK and c-Src are important regulators of cell adhesion and are linked to various pathologies, nevertheless, more comprehensive research on these proteins would be a significant step forward in the development of effective therapies for the diseases associated with them.

Molecular correlates of social adversity in breast cancer.

48 Background: Neighborhood disadvantage (ND) is associated with shorter breast cancer (BCa) survival independent of individual, tumor, and treatment factors, suggesting more aggressive tumor biology in women from disadvantaged neighborhoods. This study evaluates how differential DNA methylation (DNAm), gene expression, and biologic pathways are wired with each other to delineate the regulatory landscape of ND on BCa. Methods: We leveraged 55 geocoded ER+/HER2- BCa samples from Hispanic White women enrolled in a prospective genomic-epidemiologic cohort study. Objective ND was evaluated using the Area Deprivation Index (ADI) and subjective ND was evaluated using the patient-reported Neighborhood Social Environment Adversity Survey and the Everyday Expanded Discrimination Survey. We analyzed the association between ND and (1) DNAm, (2) RNA transcription and miRNAs, and (3) blood concentration levels of DNAm co-factors (B12 and folate) from the same patient. To evaluate how the DNAm/expressed pathways are wired with each other to delineate the regulatory landscape of ND in these tumors, we performed correlation analyses among CpGs, genes, and miRNAs in the same topologically associated domain (TAD). We used Spearman correlation as our metric and adjusted the resulting p-values to FDR values. Results: The cohort was divided into low ND (ADI<5; 31%) and a high ND (ADI>=5; 69%). There were no significant differences between groups by age, race/ethnicity, genetic ancestry, BMI, smoking/alcohol, subtype, stage, or OncotypeDX scores. We discovered that high ND exhibits epigenetic deregulation of immune pathways, consistent with our findings of lower circulating B12 in high ND, suggesting activation of immune pathways through reduced systemic availability of methyl donors. RNA-seq identified higher tumor infiltration of immune cells in patients from high ND (e.g., Interferon alpha and gamma responses and inflammatory responses) consistent with aggressive biology. Estrogen response genes were downregulated suggesting that patients from high ND may develop estrogen-resistant tumors. Higher subjective ND scores discovered epigenetic changes on cell adhesion and calcium signaling genes, along with gene expression of E2F targets and cell cycle’s G2M checkpoint, indicative of a more proliferative/stemness signature. TAD analysis discovered significant developmental, immune, and signaling pathways when correlating DNAm with gene expression (e.g., estrogen response and EMT). Conclusions: In this multi-omic matched cohort, we discovered differentially methylated/expressed pathways, consistent with aggressive biology, wired with each other to identify a novel regulatory landscape of ND on BCa. These findings can inform interventions such as improved access to healthy nutrition (B12) in ND/food deserts or targeted stress-reduction interventions based on our survey findings to ultimately reverse aggressive tumor biology and reduce BCa disparities by ND.

Research Progress into the Biological Functions of IFITM3.

Interferon-induced transmembrane proteins (IFITMs) are upregulated by interferons. They are not only highly conserved in evolution but also structurally consistent and have almost identical structural domains and functional domains. They are all transmembrane proteins and have multiple heritable variations in genes. The IFITM protein family is closely related to a variety of biological functions, including antiviral immunity, tumor formation, bone metabolism, cell adhesion, differentiation, and intracellular signal transduction. The progress of the research on its structure and related functions, as represented by IFITM3, is reviewed.

Family-Wide Photoproximity Profiling of Integrin Protein Social Networks in Cancer.

Integrin family transmembrane receptors mediate dynamic interactions between cells and their extracellular microenvironment. The heterogeneous interaction partners of integrins directly regulate cell adhesion, motility, proliferation, and intracellular signaling. Despite the recognized importance of protein-protein interactions and the formation of signaling hubs around integrins, the ability to detect and quantify these dynamic binding partners with high spatial and temporal resolution remains challenging. Here, we developed an integrin-family-directed quantitative photoproximity protein interaction (PhotoPPI) profiling method to detect and quantify native integrin-centered protein social networks on live cells and tissues without the need for genetic manipulation, antibodies, or non-physiologic cell culture conditions. We drafted quantitative maps of integrin-centered protein social networks, highlighting conserved and unique binding partners between different cell types and cellular microenvironments. Comparison of integrin social networks in cancer cell lines of diverse tissue of origin and disease state identified specific AND-gate binding partners involved cell migration, microenvironmental interactions and proliferation that serve as markers of tumor cell metastatic state. Finally, we identified unique combinations - or barcodes - of integrin-proximal proteins on the surface of pre- and post-metastatic triple negative breast cancer (TNBC) cells whose expression strongly correlate with both positive and negative disease progression and outcomes in TNBC patients. Taken together, these data provide the first family-wide high-resolution maps of native protein interactors on live cells and identify dynamic integrin-centered social networks as potential AND-gate markers of cell identity, microenvironmental context and disease state.

High expression of CREM is associated with poor prognosis in gastric cancer patients

To analyze the expression of CREM in gastric cancer (GC) and its correlation with prognosis of the patients. TCGA and GEO databases were used to analyze the expression levels of CREM mRNA in GC and adjacent tissues. Immunohistochemistry was used to examine the expression of CREM protein in 43 pairs of GC and adjacent tissues, and the correlation of CREM expression with clinicopathological features of the patients was analyzed. Kaplan-Meier survival analysis was used to explore the relationship between CREM expression and survival of GC patients. LinkedOmics database was used to annotate the GO function and KEGG pathway enrichment of CREM-related genes. Database analysis showed that CREM was highly expressed in GC tissues (P < 0.05) and positively correlated with poor prognosis in GC patients (P=0.01). Immunohistochemistry results showed significantly higher CREM expression in GC tissues than in paired adjacent tissues (P < 0.0001), and its expression level was correlated with T-stage and N-stage of the tumor (P < 0.05). The overall survival of GC patients with high expression of CREM was shorter (RR=4.02, P=0.0046). Gene enrichment analysis showed that high CREM expression promotes occurrence and progression of GC very likely through the cell adhesion signaling pathway. CREM is highly expressed in GC, and its high expression is associated with a poor prognosis of GC patients, suggesting the potential of CREM to serve as a prognostic indicator for GC.

ROS-mediated ITGB5 promotes tongue squamous cell carcinoma metastasis through epithelial mesenchymal transition and cell adhesion signal pathway

PurposeIntegrin β5 (ITGB5) is an integrin β subunit member widely expressed in the human bodies, especially in cancer cells and tissues, which is a key factor in promoting tumor metastasis. In this study we investigated the differential expression of ITGB5 in tongue squamous cell carcinoma (TSCC), especially in those with lymph node metastasis, and revealed the possible mechanism.MethodsThe expression of ITGB5 in TSCC was analyzed by database and verified by immunohistochemistry through 135 TSCC patients’ tissue sections from Sun Yat-sen Memorial Hospital and Guangzhou First People’s Hospital. The relationship between ITGB5 and lymph node metastasis or prognosis was analyzed retrospectively. The effects of ITGB5 on TSCC cells were examined through knocking down or overexpression and its possible regulator and signal pathway were explored.ResultsThe expression of ITGB5 in TSCC was higher than that in adjacent tissue, and the expression in patients with lymph node metastasis was higher than that in patients without lymph node metastasis. The high expression of ITGB5 predicted a worse prognosis. Knock down of ITGB5 suppressed invasion and migration of TSCC cells, while overexpression of ITGB5 contributed to invasion and migration. Reactive oxygen species (ROS) regulated epithelial mesenchymal transition (EMT), and we further verified that ROS enhanced the expression of ITGB5 to promote the metastasis of TSCC. Mechanistically, ITGB5 functions through cell adhesion signal pathway.ConclusionThe increased expression of ITGB5 in tongue squamous cell carcinoma with lymph node metastasis may be a potential target for evaluating lymph node metastasis and worse prognosis of tongue squamous cell carcinoma. Scavenge of ROS or knock down of ITGB5 may be the strategies to overcome metastasis of TSCC.

Transdermal characteristic study of bovine sialoglycoproteins with anti-skin aging and accelerating skin wound healing.

Sialoglycoproteins play important roles in various biological processes, including cell adhesion, immune response, and cell signaling. Our previous studies indicated that the bovine sialoglycoproteins could be developed as a reagent against skin aging and as a new candidate for accelerating skin wound healing as well as inhibiting scar formation. However, transdermal characteristic of the bovine sialoglycoproteins is still unknown. This study investigated the transdermal permeation of the bovine sialoglycoproteins through porcine skin using the Franz diffusion cell method. Our study showed that the bovine sialoglycoproteins could penetrate through the porcine skin with a linear permeation pattern described by the regression equation N% = 11.49 t-3.858, with a high coefficient of determination (R2 = 0.9903). The histochemical results demonstrated the widespread distribution of the bovine sialoglycoproteins between the epidermal and dermal layers, which suggesting parts of the bovine sialoglycoproteins had ability to traverse the epidermal barrier. The results of the lectin microarrays indicated highly enriched glycopatterns on the bovine sialoglycoproteins, which also appeared in permeated porcine skin. The LC-MS/MS analysis further showed that the bovine sialoglycoproteins were composed of approximately 100 proteins with molecular weight ranging from 748.4 kDa to 10 kDa, and there were 23 specific bovine sialoglycoproteins with molecular weight ranging from 69.2 kDa to 10 kDa to be characterized in permeated porcine skin. Parts of the bovine sialoglycoproteins with molecular weight less than 69.2 kDa had ability to traverse the epidermal barrier. Understanding the permeation characteristics of the bovine sialoglycoproteins for developing innovative formulations with therapeutic benefits, contributing to advancements in cosmetic and dermatological fields.

The receptor protein tyrosine phosphatase PTPRK promotes intestinal repair and catalysis-independent tumour suppression.

PTPRK is a receptor tyrosine phosphatase that is linked to the regulation of growth factor signalling and tumour suppression. It is stabilized at the plasma membrane by trans homophilic interactions upon cell-cell contact. PTPRK regulates cell-cell adhesion but is also reported to regulate numerous cancer-associated signalling pathways. However, the signalling mechanism of PTPRK remains to be determined. Here, we find that PTPRK regulates cell adhesion signalling, suppresses invasion and promotes collective, directed migration in colorectal cancer cells. In vivo, PTPRK supports recovery from inflammation-induced colitis. In addition, we confirm that PTPRK functions as a tumour suppressor in the mouse colon and in colorectal cancer xenografts. PTPRK regulates growth factor and adhesion signalling, and suppresses epithelial to mesenchymal transition (EMT). Contrary to the prevailing notion that PTPRK directly dephosphorylates EGFR, we find that PTPRK regulation of both EGFR and EMT is independent of its catalytic function. This suggests that additional adaptor and scaffold functions are important features of PTPRK signalling.

Mechanism underlying the role of integrin α3β1 in adhesive dysfunction between thyroid cells induced by diesel engine exhaust particles

The role and mechanisms of DEP exposure on thyroid injury are not yet clear. This study explores thyroid damage induced by in vivo DEP exposure using a mouse model. This study has observed alterations in thyroid follicular architecture, including rupture, colloid overflow, and the formation of voids. Additionally, there was a significant decrease in the expression levels of proteins involved in thyroid hormone synthesis, such as thyroid peroxidase and thyroglobulin, their trend of change is consistent with the damage to the thyroid structure. Serum levels of triiodothyronine and tetraiodothyronine were raise. However, the decrease in TSH expression suggests that the function of the HPT axis is unaffected. To delve deeper into the intrinsic mechanisms of thyroid injury, we performed KEGG pathway enrichment analysis, which revealed notable alterations in the cell adhesion signaling pathway. Our immunofluorescence results show that DEP exposure impairs thyroid adhesion, and integrin α3β1 plays an important role. CD151 binds to α3β1, promoting multimolecular complex formation and activating adhesion-dependent small GTPases. Our in vitro model has confirmed the pivotal role of integrin α3β1 in thyroid cell adhesion, which may be mediated by the CD151/α3β1/Rac1 pathway. In summary, exposure to DEP disrupts the structure and function of the thyroid, a process that likely involves the regulation of cell adhesion through the CD151/α3β1/Rac1 pathway, leading to glandular damage.

Identifying Hub Genes Related to Vascular Endothelial Cell Permeability Through Bioinformatics and Verification.

In this study, we aimed to identify the hub genes responsible for increased vascular endothelial cell permeability. We applied the weighted Gene Expression Omnibus (GEO) database to mine dataset GSE178331 and ob-tained the most relevant high-throughput sequenced genes for an increased permeability of vascular endothelial cells due to inflammation. We constructed two weighted gene co-expression network analysis (WGCNA) networks, and the differential expression of high-throughput sequenced genes related to endothelial cell permeability were screened from the GEO database. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis were performed on the differential genes. Their degree values were obtained from the topological properties of protein-protein interaction (PPI) networks of differential genes, and the hub genes associated with an increased endothelial cell permeability were analyzed. Reverse transcription-polymerase chain reaction (RT-PCR) and western blotting techniques were used to detect the presence of these hub genes in TNF-α induced mRNA and the protein expression in endothelial cells. In total, 1,475 differential genes were mainly enriched in the cell adhesion and TNF-α signaling pathway. With TNF-α inducing an increase in the endothelial cell permeability and significantly increasing mRNA and protein expression levels, we identified three hub genes, namely PTGS2, ICAM1, and SNAI1. There was a significant difference in the high-dose TNF-α group and in the low-dose TNF-α group compared to the control group, in the endothelial cell permeability experiment (p = 0.008 vs. p = 0.02). Measurement of mRNA and protein levels of PTGS2, ICAM1, and SNAI1 by western blotting analysis showed that there was a significant impact on TNF-α and that there was a significant dose-dependent relationship (p < 0.05 vs. p < 0.01). The three hub genes identified through bioinformatics analyses in the present study may serve as biomarkers of increased vascular endothelial cell permeability. The findings offer valuable insights into the progress and mechanism of vascular endothelial cell permeability.