AI Article Synopsis
Article Abstract
The alpha5beta1 integrin represent a new therapeutic target for glioblastoma, which are malignant brain tumors difficult to cure with conventional therapies. Glioblastoma are known to be highly resistant to chemotherapy. We, therefore, investigated whether blocking alpha5beta1 integrin with specific nonpeptidic antagonists concomitantly with chemotherapy (ellipticine and temozolomide) may impact the response to chemotherapy of human glioblastoma. Here we show that inhibiting alpha5beta1 integrin with 2 selective ligands (SJ749 and K34c) decreases chemotherapy-induced premature senescence and facilitates cell apoptosis in a functional p53 background (U87MG cells). When p53 is mutated and inactive (U373 cells), chemotherapy induces p53-independent cell apoptosis instead of senescence that is not improved by integrin antagonists. Silencing p53 in U87MG cells with siRNA as well as evaluating HCT116 p53+/+ and p53-/- colon carcinoma cell behavior support the hypothesis of an as yet unknown effect of alpha5beta1 integrin antagonists on the control of chemotherapy-induced premature senescence and apoptosis. alpha5beta1 integrin antagonists modulate the p53 signaling induced by chemotherapy. Our results highlight a new role of the alpha5beta1 integrin in the control of glioblastoma aggressiveness and responsiveness to chemotherapy, which may have a crucial impact in the clinical management of patients suffering from brain tumors.
Download full-text PDF |
Source |
|---|---|
| http://dx.doi.org/10.1002/ijc.25187 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
SPP1-ITGα5/β1 Accelerates Calcification of Nucleus Pulposus Cells by Inhibiting Mitophagy via Ubiquitin-Dependent PINK1/PARKIN Pathway Blockade.
Adv Sci (Weinh)
December 2024
Department of Orthopedic, Qilu Hospital of Shandong University, Jinan, Shandong, 250012, China.
Low back pain (LBP) caused by nucleus pulposus degeneration and calcification leads to great economic and social burden worldwide. Unexpectedly, no previous studies have demonstrated the association and the underlying mechanism between nucleus pulposus tissue degeneration and calcification formation. Secreted Phosphoprotein 1 (SPP1) exerts crucial functions in bone matrix mineralization and calcium deposition.
View Article and Find Full Text PDFThe novel ECM protein SNED1 mediates cell adhesion via the RGD-binding integrins α5β1 and αvβ3.
J Cell Sci
December 2024
Department of Physiology and Biophysics, University of Illinois Chicago, Illinois, 60612, USA.
The extracellular matrix (ECM) is a complex meshwork comprising over 100 proteins. It serves as an adhesive substrate for cells and, hence, plays critical roles in health and disease. We have recently identified a novel ECM protein, SNED1, and have found that it is required for neural crest cell migration and craniofacial morphogenesis during development and in breast cancer, where it is necessary for the metastatic dissemination of tumor cells.
View Article and Find Full Text PDFO-GlcNAcylation stabilized WTAP promotes GBM malignant progression in an N6-methyladenosine-dependent manner.
Neuro Oncol
December 2024
Department of Neurosurgery, Qilu Hospital of Shandong University, Cheeloo College of Medicine and Institute of Brain and Brain-Inspired Science, Shandong University, Jinan 250012, Shandong, China.
Background: Interactions between mesenchymal glioblastoma stem cells (MES GSCs) and myeloid-derived macrophages (MDMs) shape the tumor-immunosuppressive microenvironment (TIME), promoting the progression of glioblastoma (GBM). N6-methyladenosine (m6A) plays important roles in the tumor progression. However, the mechanism of m6A in shaping the TIME of GBM remains elusive.
View Article and Find Full Text PDFEndothelial Angpt2 Promotes Adipocyte Progenitor Cells Maturation to Increase Visceral Adipose Tissue Accumulation.
Diabetes Metab Res Rev
January 2025
Department of General Surgery, The Third Xiangya Hospital, Central South University, Changsha, China.
Aims: Visceral adipose tissue (VAT) accumulation is essential for the occurrence and development of obesity and related metabolic diseases. Currently, the specific mechanism of VAT accumulation is still unclear.
Materials And Methods: We searched the Gene Expression Omnibus database to obtain single-cell RNA sequencing (scRNAseq) data for VAT in patients with a normal body mass index (BMI), obesity, or morbid obesity.
A Novel P-III Metalloproteinase from Venom Degrades Extracellular Matrix Proteins, Inhibits Platelet Aggregation, and Disrupts Endothelial Cell Adhesion via α5β1 Integrin Receptors to Arginine-Glycine-Aspartic Acid (RGD)-Containing Molecules.
Toxins (Basel)
November 2024
Laboratório de Matriz Extracelular e Biotecnologia de Venenos, Universidade Federal do Paraná, UFPR, Curitiba 81531-980, Brazil.
Article Synopsis
- Viperid snake venoms contain metalloproteinases like barnettlysin-III (Bar-III), which cause bleeding and disrupt blood clotting and tissue integrity in victims.
- Bar-III, a specific type of metalloproteinase, has been characterized in terms of its properties, including its activity being enhanced by calcium and inhibited by zinc, and its ability to degrade important blood and tissue proteins.
- The study also highlights Bar-III’s effects on platelets and endothelial cells, suggesting that it affects platelet aggregation and cell adhesion, providing insights that could lead to new treatments for snakebite envenomation.
Want AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!