6 research outputs found
Armus dual roles in autophagy and E-cadherin degradation: distinct partners, regulation and implications for cancer patients
Cancer is one of the leading causes of mortality worldwide. Invasion, metastasis and apoptotic evasion are cancer hallmarks. Tumour cell metastasis requires loss of E-cadherin cell-cell adhesion receptor. Apoptotic evasion can be mediated by up-regulation of autophagy, which maintains cellular energy during metabolic stress in cancer cells. Armus is a TBC/RabGAP protein that regulates both E-cadherin degradation and autophagy by controlling lysosome fusion with late vesicular compartments or autophagosomes. Understanding Armus function in these degradative processes during tumourigenesis may lead to combinatorial inhibition of oncogenic pathways and novel therapeutic targets. Here I address: (i) whether Armus participates in E-cadherin deregulation downstream of oncogenes, (ii) potential mechanisms through which Armus can switch between its function at junctions and autophagosomes and (iii) potential strategies to inhibit Armus intracellular localisation. I found that Armus is involved in Src and H-Ras disruption of E-cadherin junctions in keratinocytes. Armus binds to α-catenin at junctions, while at autophagosomes Armus interacts with autophagy marker, LC3. Incubation with Armus peptides containing LC3-interacting motifs partially blocks Armus function in autophagy. Mutation of the specific residues mediating α-catenin association reduces Armus localisation at cell-cell contacts. The close juxtaposition of LC3 and α-catenin binding at PH domain at Armus N-terminus may suggest additional roles. Armus N-terminus and RabGAP domain interact directly, and residue K480 is critical for binding. This intramolecular interaction may form a closed conformation, and Armus activation may require the release of this auto-inhibition. It is tempting to suggest that protein interactions at the PH domain such as LC3 and α-catenin may modulate Armus auto-inhibition. Alternatively, the phosphoinositide repertoire interacting with the PH domain may contribute to Armus intracellular distribution and activation. Further insights into Armus activation may provide greater understanding of its function in distinct cellular events with implications for tumourigenesis.Open Acces
Trends and Advances in Electrochemiluminescence Nanobiosensors
The rapid and increasing use of the nanomaterials (NMs), nanostructured materials (NSMs), metal nanoclusters (MNCs) or nanocomposites (NCs) in the development of electrochemiluminescence (ECL) nanobiosensors is a significant area of study for its massive potential in the practical application of nanobiosensor fabrication. Recently, NMs or NSMs (such as AuNPs, AgNPs, Fe3O4, CdS QDs, OMCs, graphene, CNTs and fullerenes) or MNCs (such as Au, Ag, and Pt) or NCs of both metallic and non-metallic origin are being employed for various purposes in the construction of biosensors. In this review, we have selected recently published articles (from 2014–2017) on the current development and prospects of label-free or direct ECL nanobiosensors that incorporate NCs, NMs, NSMs or MNCs
Electrochemical Nanoaptasensor Based on Graphitic Carbon Nitride/Zirconium Dioxide/Multiwalled Carbon Nanotubes for Matrix Metalloproteinase‑9 in Human Serum and Saliva
In this study, a nanocomposite was synthesized by incorporating
graphitic carbon nanosheets, carboxyl-functionalized multiwalled carbon
nanotubes, and zirconium oxide nanoparticles. The resulting nanocomposite
was utilized for the modification of a glassy carbon electrode. Subsequently,
matrix metalloproteinase aptamer (AptMMP‑9) was
immobilized onto the electrode surface through the application of
ethyl-3-(3-(dimethylamino)propyl)carbodiimide hydrochloride-N-hydroxysuccinimide (EDC–NHS) chemistry. Morphological
characterization of the nanomaterials and the nanocomposite was performed
using field-emission scanning electron microscopy (FESEM). The nanocomposite
substantially increased the electroactive surface area by 205%, facilitating
enhanced immobilization of AptMMP‑9. The efficacy
of the biosensor was evaluated using cyclic voltammetry (CV) and differential
pulse voltammetry (DPV). Under optimal conditions, the fabricated
sensor demonstrated a broad range of detection from 50 to 1250 pg/mL
with an impressive lower limit of detection of 10.51 pg/mL. In addition,
the aptasensor exhibited remarkable sensitivity, stability, excellent
selectivity, reproducibility, and real-world applicability when tested
with human serum and saliva samples. In summary, our developed aptasensor
exhibits significant potential as an advanced biosensing tool for
the point-of-care quantification of MMP-9, promising advancements
in biomarker detection for practical applications
Colorimetric Nucleic Acid Detection on Paper Microchip Using Loop Mediated Isothermal Amplification and Crystal Violet Dye
Nucleic
acid detection is of paramount importance in monitoring
of microbial pathogens in food safety and infectious disease diagnostic
applications. To address these challenges, a rapid, cost-effective
label-free technique for nucleic acid detection with minimal instrumentations
is highly desired. Here, we present paper microchip to detect and
quantify nucleic acid using colorimetric sensing modality. The extracted
DNA from food samples of meat as well as microbial pathogens was amplified
utilizing loop-mediated isothermal amplification (LAMP). LAMP amplicon
was then detected and quantified on a paper microchip fabricated in
a cellulose paper and a small wax chamber utilizing crystal violet
dye. The affinity of crystal violet dye toward dsDNA and positive
signal were identified by changing the color from colorless to purple.
Using this method, detection of Sus scrofa (porcine) and Bacillus subtilis (bacteria) DNA was possible at
concentrations as low as 1 pg/μL (3.43 × 10 <sup>–1</sup> copies/μL) and 10 pg/μL (2.2 × 10<sup>3</sup> copies/μL),
respectively. This strategy can be adapted for detection of other
DNA samples, with potential for development of a new breed of simple
and inexpensive paper microchip at the point-of-need