scholarly journals The Role of Heparanase and Sulfatases in the Modification of Heparan Sulfate Proteoglycans within the Tumor Microenvironment and Opportunities for Novel Cancer Therapeutics

2014 ◽  
Vol 4 ◽  
Author(s):  
Edward Hammond ◽  
Ashwani Khurana ◽  
Viji Shridhar ◽  
Keith Dredge
Keyword(s):  
Tumor Microenvironment ◽  
Heparan Sulfate ◽  
Cancer Therapeutics ◽  
Heparan Sulfate Proteoglycans

scholarly journals Role of heparan sulfate proteoglycans in the binding and uptake of apolipoprotein E-enriched remnant lipoproteins by cultured cells

1993 ◽  
Vol 268 (14) ◽  
pp. 10160-10167
Author(s):  
Z.S. Ji ◽  
W.J. Brecht ◽  
R.D. Miranda ◽  
M.M. Hussain ◽  
T.L. Innerarity ◽  
...  
Keyword(s):  
Apolipoprotein E ◽  
Heparan Sulfate ◽  
Cultured Cells ◽  
Heparan Sulfate Proteoglycans ◽  
Remnant Lipoproteins

scholarly journals Role of Cellular Heparan Sulfate Proteoglycans in Infection of Human Adenovirus Serotype 3 and 35

2008 ◽  
Vol 4 (10) ◽  
pp. e1000189 ◽  
Author(s):  
Sebastian Tuve ◽  
Hongjie Wang ◽  
Jeffrey D. Jacobs ◽  
Roma C. Yumul ◽  
David F. Smith ◽  
...  
Keyword(s):  
Heparan Sulfate ◽  
Human Adenovirus ◽  
Heparan Sulfate Proteoglycans ◽  
Adenovirus Serotype

scholarly journals MicroRNAs as Emerging Regulators of Signaling in the Tumor Microenvironment

Cancers ◽  
2020 ◽  
Vol 12 (4) ◽  
pp. 911 ◽  
Author(s):  
Shahzad Nawaz Syed ◽  
Bernhard Brüne
Keyword(s):  
Tumor Microenvironment ◽  
Signaling Pathways ◽  
Target Identification ◽  
Cancer Therapeutics ◽  
Protein Translation ◽  
Transcriptional Gene Silencing ◽  
Post Transcriptional Gene Silencing ◽  
Cancer Initiation ◽  
Regulate Protein

A myriad of signaling molecules in a heuristic network of the tumor microenvironment (TME) pose a challenge and an opportunity for novel therapeutic target identification in human cancers. MicroRNAs (miRs), due to their ability to affect signaling pathways at various levels, take a prominent space in the quest of novel cancer therapeutics. The role of miRs in cancer initiation, progression, as well as in chemoresistance, is being increasingly investigated. The canonical function of miRs is to target mRNAs for post-transcriptional gene silencing, which has a great implication in first-order regulation of signaling pathways. However, several reports suggest that miRs also perform non-canonical functions, partly due to their characteristic non-coding small RNA nature. Examples emerge when they act as ligands for toll-like receptors or perform second-order functions, e.g., to regulate protein translation and interactions. This review is a compendium of recent advancements in understanding the role of miRs in cancer signaling and focuses on the role of miRs as novel regulators of the signaling pathway in the TME.

scholarly journals The Uptake of Lipoprotein-Borne Phylloquinone (Vitamin K1) by Osteoblasts and Osteoblast-Like Cells: Role of Heparan Sulfate Proteoglycans and Apolipoprotein E

2002 ◽  
Vol 17 (3) ◽  
pp. 426-433 ◽  
Author(s):  
Paul Newman ◽  
Fiona Bonello ◽  
Anthony S. Wierzbicki ◽  
Peter Lumb ◽  
Geoffrey F. Savidge ◽  
...  
Keyword(s):  
Apolipoprotein E ◽  
Heparan Sulfate ◽  
Heparan Sulfate Proteoglycans ◽  
Vitamin K1

Intracellular Responses of Glial Cells To Monomeric Tau Protein Are Closely Mediated By Heparan Sulfate Proteoglycans (HSPGs)

2021 ◽  
Author(s):  
Liqing Song ◽  
Daniel E. Oseid ◽  
Evan A. Wells ◽  
Troy Coaston ◽  
Anne S Robinson
Keyword(s):  
Gene Expression ◽  
Heparan Sulfate ◽  
Glial Cells ◽  
Neurofibrillary Tangles ◽  
Tau Protein ◽  
Intracellular Signaling ◽  
Heparan Sulfate Proteoglycans ◽  
C6 Glioma Cells ◽  
Dependent Manner

Abstract The conversion of soluble tau protein to insoluble, hyperphosphorylated neurofibrillary tangles is a major hallmark leading to neuronal death observed in neurodegenerative tauopathies. Recent work suggests that extracellular, soluble tau binds to negatively charged heparan sulfate proteoglycans (HSPGs) available on the cell surface. In addition, LRP1 has recently been recognized as a major tau receptor, mediating tau uptake and spread. We hypothesized based on this data that monomeric tau would be endocytosed in both an HSPG- and LRP-dependent manner, activating intracellular signaling pathways that would regulate cellular phenotypes. Using live-cell confocal microscopy and flow cytometry, we show that soluble 0N4R monomers were rapidly endocytosed by SH-SY5Y and C6 glioma cells, via actin-dependent macropinocytosis. We also demonstrated the crucial role of HSPGs and LRP1 in cellular endocytosis of monomeric tau by observing reduced tau uptake in C6 glial cells with genetic knockouts of xylosyltransferase-1 – a key enzyme in HSPG synthesis – and LRP1. An ERK1/2 inhibition experiment showed that inhibiting the MEK-ERK1/2 signaling pathway attenuated IL-6 and IL-1β gene expression but not TNF-α . An LRP1 knockdown experiment led to an attenuated propensity for tau uptake and further elevated IL-6 gene expression. Collectively, our data suggest that tau has multiple extracellular binding partners that mediate its internalization through distinct mechanisms. Additionally, this study demonstrates the important role of both HSPG and LRP1 in regulating cellular immune responses to tau protein monomer, which provides a novel target for alleviating the neuroinflammatory environment before the formation of neurofibrillary tangles.

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