scholarly journals Functions and Inhibition of Galectin-7, an Emerging Target in Cellular Pathophysiology

Biomolecules ◽  
2021 ◽  
Vol 11 (11) ◽  
pp. 1720
Author(s):  
Nishant V. Sewgobind ◽  
Sanne Albers ◽  
Roland J. Pieters

Galectin-7 is a soluble unglycosylated lectin that is able to bind specifically to β-galactosides. It has been described to be involved in apoptosis, proliferation and differentiation, but also in cell adhesion and migration. Several disorders and diseases are discussed by covering the aforementioned biological processes. Structural features of galectin-7 are discussed as well as targeting the protein intracellularly or extracellularly. The exact molecular mechanisms that lie behind many biological processes involving galectin-7 are not known. It is therefore useful to come up with chemical probes or tools in order to obtain knowledge of the physiological processes. The objective of this review is to summarize the roles and functions of galectin-7 in the human body, providing reasons why it is necessary to design inhibitors for galectin-7, to give the reader structural insights and describe its current inhibitors.

1996 ◽  
Vol 29 (1) ◽  
pp. 91-117 ◽  
Author(s):  
Peter B. Garland

Implementation and regulation of the molecular mechanisms underlying biological processes is dependent on direct interactions between biological molecules. These interactions are characterised by specific binding between at least one molecule and another, and for binding to occur the molecules must be able to come close enough to each other to make contact. One of the partners in the interaction is invariably a macromolecule (e.g. protein or DNA) or an assembly of large size, such as a lipid bilayer. The interaction may take place with the partners in solution, or with at least one attached to a biological surface (e.g. a membrane) or a very large structure such as a chromosome. Where the partners are part of a membrane or other large structure then there must be a mechanism, such as lateral diffusion in the plane of the membrane, that permits them to come together close enough for interaction.


2021 ◽  
Vol 134 (5) ◽  
Author(s):  
Jiamin Yi ◽  
Jiangling Peng ◽  
Wenping Yang ◽  
Guoqiang Zhu ◽  
Jingjing Ren ◽  
...  

ABSTRACT The protease 3C is encoded by all known picornaviruses, and the structural features related to its protease and RNA-binding activities are conserved; these contribute to the cleavage of viral polyproteins and the assembly of the viral RNA replication complex during virus replication. Furthermore, 3C performs functions in the host cell through its interaction with host proteins. For instance, 3C has been shown to selectively ‘hijack’ host factors involved in gene expression, promoting picornavirus replication, and to inactivate key factors in innate immunity signaling pathways, inhibiting the production of interferon and inflammatory cytokines. Importantly, 3C maintains virus infection by subtly subverting host cell death and modifying critical molecules in host organelles. This Review focuses on the molecular mechanisms through which 3C mediates physiological processes involved in virus–host interaction, thus highlighting the picornavirus-mediated pathogenesis caused by 3C.


2018 ◽  
Author(s):  
Dennis Klug ◽  
Sarah Goellner ◽  
Julia Sattler ◽  
Leanne Strauss ◽  
Jessica Kehrer ◽  
...  

AbstractCell-cell and cell-substrate adhesion is critical for many functions in life. In eukaryotes, I-domains mediate functions as divergent as tissue traversal by malaria-causing Plasmodium parasites as well as cell adhesion and migration by human leucocytes. The I-domain containing protein TRAP is important for Plasmodium sporozoite motility and invasion. Here we show that the I-domain of TRAP is required to mediate adhesional properties which can be partially preserved when the native I-domain is replaced by I-domains from human integrins or from an apicomplexan parasite that does not infect insects. By putting in vivo data and structural features in perspective we conclude that polyspecificity and positive charge around the ligand binding site of the I-domain are important for TRAP function. Our data suggest a highly preserved functionality of I-domains across eukaryotic evolution that is used by apicomplexan parasites to invade a broad range of tissues in a variety of hosts.


Biomedicines ◽  
2021 ◽  
Vol 9 (9) ◽  
pp. 1102
Author(s):  
Giuseppe La Verde ◽  
Valeria Artiola ◽  
Valeria Panzetta ◽  
Mariagabriella Pugliese ◽  
Paolo A. Netti ◽  
...  

The cytoskeleton is involved in several biological processes, including adhesion, motility, and intracellular transport. Alterations in the cytoskeletal components (actin filaments, intermediate filaments, and microtubules) are strictly correlated to several diseases, such as cancer. Furthermore, alterations in the cytoskeletal structure can lead to anomalies in cells’ properties and increase their invasiveness. This review aims to analyse several studies which have examined the alteration of the cell cytoskeleton induced by ionizing radiations. In particular, the radiation effects on the actin cytoskeleton, cell adhesion, and migration have been considered to gain a deeper knowledge of the biophysical properties of the cell. In fact, the results found in the analysed works can not only aid in developing new diagnostic tools but also improve the current cancer treatments.


2018 ◽  
Author(s):  
Stacy A. Malaker ◽  
Kayvon Pedram ◽  
Michael J. Ferracane ◽  
Elliot C. Woods ◽  
Jessica Kramer ◽  
...  

<div> <div> <div> <p>Mucins are a class of highly O-glycosylated proteins that are ubiquitously expressed on cellular surfaces and are important for human health, especially in the context of carcinomas. However, the molecular mechanisms by which aberrant mucin structures lead to tumor progression and immune evasion have been slow to come to light, in part because methods for selective mucin degradation are lacking. Here we employ high resolution mass spectrometry, polymer synthesis, and computational peptide docking to demonstrate that a bacterial protease, called StcE, cleaves mucin domains by recognizing a discrete peptide-, glycan-, and secondary structure- based motif. We exploited StcE’s unique properties to map glycosylation sites and structures of purified and recombinant human mucins by mass spectrometry. As well, we found that StcE will digest cancer-associated mucins from cultured cells and from ovarian cancer patient-derived ascites fluid. Finally, using StcE we discovered that Siglec-7, a glyco-immune checkpoint receptor, specifically binds sialomucins as biological ligands, whereas the related Siglec-9 receptor does not. Mucin-specific proteolysis, as exemplified by StcE, is therefore a powerful tool for the study of glycoprotein structure and function and for deorphanizing mucin-binding receptors. </p> </div> </div> </div>


2020 ◽  
Vol 26 (15) ◽  
pp. 1729-1741 ◽  
Author(s):  
Seyed H. Shahcheraghi ◽  
Venant Tchokonte-Nana ◽  
Marzieh Lotfi ◽  
Malihe Lotfi ◽  
Ahmad Ghorbani ◽  
...  

: Glioblastoma (GBM) is the most common and malignant astrocytic glioma, accounting for about 90% of all brain tumors with poor prognosis. Despite recent advances in understanding molecular mechanisms of oncogenesis and the improved neuroimaging technologies, surgery, and adjuvant treatments, the clinical prognosis of patients with GBM remains persistently unfavorable. The signaling pathways and the regulation of growth factors of glioblastoma cells are very abnormal. The various signaling pathways have been suggested to be involved in cellular proliferation, invasion, and glioma metastasis. The Wnt signaling pathway with its pleiotropic functions in neurogenesis and stem cell proliferation is implicated in various human cancers, including glioma. In addition, the PI3K/Akt/mTOR pathway is closely related to growth, metabolism, survival, angiogenesis, autophagy, and chemotherapy resistance of GBM. Understanding the mechanisms of GBM’s invasion, represented by invasion and migration, is an important tool in designing effective therapeutic interventions. This review will investigate two main signaling pathways in GBM: PI3K/Akt/mTOR and Wnt/beta-catenin signaling pathways.


Author(s):  
Qiong Luo ◽  
Suyun Zhang ◽  
Donghuan Zhang ◽  
Rui Feng ◽  
Nan Li ◽  
...  

Background: Gastric cancer(GC) is currently one of the major malignancies that threatens human lives and health. Anlotinib is a novel small-molecule that inhibits angiogenesis to exert anti-tumor effects. However, the function in gastric cancer is incompletely understood. Objective: The aim of the present study was to investigate the anti-tumor effects and molecular mechanisms of anlotinib combined with dihydroartemisinin (DHA) in SGC7901 gastric cancer cells. Method: Different concentrations of anlotinib and DHA were used to treat SGC7901 gastric cancer cells, after which cell proliferation was measured. Drug interactions of anlotinib and DHA were analyzed by the Chou-Talalay method with CompuSyn software. proliferation, apoptosis, invasion, migration, and angiogenesis were measured using the cell counting kit-8 (CCK8) assay, flow cytometry, Transwell invasion assays, scratch assays, and chicken chorioallantoic membrane (CAM) assays. proliferation-associated protein (Ki67), apoptosis-related protein (Bcl-2), and vascular endothelial growth factor A (VEGF-A) were quantified by Western bloting. Results: The combination of 2.5 μmol/L of anlotinib and 5 of μmol/L DHA was highly synergistic in inhibiting cell growth, significantly increased the apoptosis rate and suppressed obviously the invasion and migration capability and angiogenesis of gastric cancer cells. In addition, the expression levels of Ki67, Bcl-2, and VEGF-A, as well as angiogenesis, were significantly decreased in the Combination of drugs compared with in control and either drug alone. Conclusion: The combination of anlotinib and DHA showed synergistic antitumor activity, suggesting their potential in treating patients with gastric cancer.


Oncogene ◽  
2020 ◽  
Vol 39 (18) ◽  
pp. 3666-3679 ◽  
Author(s):  
Mario De Piano ◽  
Valeria Manuelli ◽  
Giorgia Zadra ◽  
Jonathan Otte ◽  
Per-Henrik D. Edqvist ◽  
...  

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