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 ^–1 copies/μL) and 10 pg/μL (2.2 × 10³ 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