Integrin αV is a prognostic marker for cutaneous squamous cell carcinoma relapse
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ABSTRACT:
PROVIDER: PRJNA975958 | ENA |
REPOSITORIES: ENA
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Project description:Early cutaneous squamous cell carcinomas (cSCCs) show epithelial differentiation features and good prognosis, whereas advanced cSCCs present mesenchymal traits and are associated with tumor relapse, metastasis, and poor survival. Prognostic biomarkers for cSCC relapse must therefore be found that accurately predict the clinical course of the disease, since established markers are suboptimal. Using mouse models of cSCC progression, we showed that the emergence of epithelial plastic cancer cells with a hybrid epithelial/mesenchymal phenotype promotes tumor progression to a mesenchymal state. These cells can be identified early on by the expression of integrin αV (ITGAV). Analysis of ITGAV expression in a cohort of primary cSCCs from patients provided prognostic information about the risk of relapse beyond current histopathological parameters. Together, our findings provide an opportunity to clinically implement ITGAV by standard immunodetection approaches and thereby improve patient stratification and therapeutic management.
2024-08-08 | GSE233382 | GEO
Project description:Thoracic aortic aneurysm (TAA) is a perilous disease that can lead to aortic dissection (AD), the pathophysiological mechanisms of which remain largely elusive. To improve our understanding of the molecular mechanism underlying TAA, we conducted a tandem mass tag (TMT)-based proteomics analysis and identified two down-regulated proteins, integrin αV, and integrin αL, in serum samples from patients with type A aortic dissection. We confirmed that integrin αV is extensively expressed in the aortic media, and its expression decreases after dissection, whereas the expression of integrin αL showed no significant alteration. Subsequently, by employing a mouse model of TAA induced by β-Aminopropionitrile (BAPN), we discovered that the mice treated with integrin αV inhibitors Cilengitide or SB273005 developed dramatically expansive ascending TAA, accompanied by exacerbated disorganization or loss of elastic fibers. Bulk RNA sequencing results further indicated that the treatment with integrin αV inhibitors exacerbates the pro-inflammatory response in mouse TAA development. These data suggest that integrin αV may be a novel target for TAA intervention. However, it also raises concerns about exposure to integrin αV inhibitors, which are conducted in serious cancer clinical trials, may pose a potential risk of developing aortic aneurysm (AA)/AD.
2025-11-23 | GSE263304 | GEO
Project description:Thoracic aortic aneurysm (TAA) is a perilous disease that can lead to aortic dissection (AD), the pathophysiological mechanisms of which remain largely elusive. To improve our understanding of the molecular mechanism underlying TAA, we conducted a tandem mass tag (TMT)-based proteomics analysis and identified two down-regulated proteins, integrin αV, and integrin αL, in serum samples from patients with type A aortic dissection. We confirmed that integrin αV is extensively expressed in the aortic media, and its expression decreases after dissection, whereas the expression of integrin αL showed no significant alteration. Subsequently, by employing a mouse model of TAA induced by β-Aminopropionitrile (BAPN), we discovered that the mice treated with integrin αV inhibitors Cilengitide or SB273005 developed dramatically expansive ascending TAA, accompanied by exacerbated disorganization or loss of elastic fibers. Bulk RNA sequencing results further indicated that the treatment with integrin αV inhibitors exacerbates the pro-inflammatory response in mouse TAA development. These data suggest that integrin αV may be a novel target for TAA intervention. However, it also raises concerns about exposure to integrin αV inhibitors, which are conducted in serious cancer clinical trials, may pose a potential risk of developing aortic aneurysm (AA)/AD.
2025-11-23 | GSE280456 | GEO
Project description:Integrin α5β1 and αv crosstalk in chemotaxis and clonogenic survival of prostate cancer cells is abrogated by a bispecific α5β1/αv antibody (BsAbα5β1/αv), which uniquely induces internalization and lysosomal degradation of target integrins. We hypothesized that the BsAbα5β1/αv inactivates pathological mechanosignaling pathways that correlate with integrin expression from patient samples. Mechanistic studies indicate that the BsAbα5β1/αv uniquely reverses YAP, beta-catenin and FAK nuclear localization compared to monospecific integrin α5β1 and αv antibody controls in basal-type androgen-receptor negative prostate cancer cells. Dual integrin αv and α5 knockdown alone phenocopied the BsAbα5β1/αv effect. Following BsAbα5β1/αv treatment, ATAC-seq studies indicated the chromatin accessibility to TEAD and AP-1 family members was markedly reduced. In vitro and in vivo RNA-seq indicated down-regulation of Myc/E2F, TGF-beta and epithelial mesenchymal transition (EMT) and upregulation of Type I and II interferon transcriptomic pathways. The BsAbα5β1/αv induced CXCL10 and CCL5 cytokine secretion, immune-infiltration of tumors, and natural-killer cell-mediated elimination of the basal-type prostate cancer xenografts in nude mice. αv integrin was highly expressed and principally correlated with the Myc signaling pathway in rapid autopsy tissue microarrays, consistent with correlative data from the SU2C metastatic castration-resistant prostate cancer and DKFZ early-onset prostate cancer cohorts. These studies connect integrin signaling with the central biology of basal-type and castration-resistant prostate cancer and define a novel therapeutic strategy that controls critical immunosuppressive pathways.
2025-06-10 | GSE292297 | GEO
Project description:Using mass spectrometry–based proteomics, we analysed the components of integrin adhesion complexes of MDA-MB-435S cells and two MDA-MB-435S-derived integrin αV-specific shRNA-expressing cell clones. Among integrins, we detected αV and β5 integrin subunits in the MDA-MB-435S adhesome, thus showing that in long term culture these cells use preferentially integrin αVβ5 for adhesion. Our data represents the first published adhesome of αVβ5 integrin heterodimer.
2020-02-17 | PXD016837 | Pride
Project description:Integrin αV as a potential target in aortic aneurysm and dissection
| PRJNA1096678 | ENA
Project description:Integrin αV as a potential target in aortic aneurysm and dissection II
| PRJNA1178646 | ENA
Project description:In the context of breast cancer metastasis study, we have shown in an in vitro model of cell migration that IGDQ-exposing (IsoLeu-Gly-Asp-Glutamine type I Fibronectin motif) monolayers (SAMs) on gold sustain the adhesion of MDA-MB-231 cells by triggering Focal Adhesion Kinase by activating integrins. Such tunable scaffolds are used to mimic the extracellular environment, inducing and controlling cell migration towards an anisotropic surface. The observed migratory behavior induced by the IGDQ-bearing peptide gradient along the surface suggests the presence of cell subpopulations: “stationary” or a “migratory” phenotype. We focused on the integrins α5(β1) and (αv)β3, already known to be implicated in cell migration. To this aim, a whole proteomic analysis was performed in beta 3 integrin (ITGB3) or alpha 5 integrin (ITGA5) knock-down MDA-MB-231, in order to highlight the pathways implied into the integrin-dependent cell migration. Our results showed that i) ITGB3 depletion influenced ITGA5 mRNA expression, ii) ITGB3 and ITGA5 were both necessary for IGDQ-mediated directional single cell migration, iii) integrin (αv)β3 was activated by IGDQ fibronectin type I motif and iv) co-regulation of retrograde transport of ITGB3 by ITGA5 is potentially necessary for directional IGDQ-mediated cell migration.
2022-11-08 | PXD024540 | Pride
Project description:TNFα secreted from macrophages increases expression of prometastatic integrin αV in gastric cancer
| PRJNA910141 | ENA
Project description:Control of basal-type prostate cancers with a bispecific integrin α5β1/αv antibody
| PRJNA1237843 | ENA