Metastasis, the hallmark of cancer propagation is attributed by the modification of phenotypic/functional behavior of cells to break attachment and migrate to distant body parts. Cancer cell-secreted microvesicles (MVs) contribute immensely in disease propagation. These nano-vesicles, generated from plasma membrane outward budding are taken up by nearby healthy cells thereby inducing phenotypic alterations in those recipient cells. Protease activated receptor 2 (PAR2), activated by trypsin, also contributes to cancer progression by increasing metastasis, angiogenesis etc. Here, we report that PAR2 activation promotes pro-metastatic MVs generation from human breast cancer cell line, MDA-MB-231. Rab5a, located at the plasma membrane plays vital roles in MVs biogenesis. We show that PAR2 stimulation promotes AKT phosphorylation which activates Rab5a by converting inactive Rab5a-GDP to active Rab5a-GTP. Active Rab5a polymerizes actin which critically regulates MVs shedding. Not only MVs generation, has this Rab5a activation also promoted cell migration and invasion. We reveal that Rab5a is over-expressed in human breast tumor specimen and contributes MVs generation in those patients. The involvement of p38 MAPK in MVs-induced cell metastasis has also been highlighted in the present study. Blockade of Rab5a activation can be a potential therapeutic approach to restrict MVs shedding and associated breast cancer metastasis.
<p>Fold and thrust belts (FTBs), formed by the collision of two continental plates, accommodate tectonic convergence through folding and faulting of crustal rocks. The effects of distributed deformation although ubiquitous in all fold-and-thrust belts, regionally occurring ductile structures are often interpreted as an outcome of localized deformation. Our study presents 3D laboratory-scale models using a viscous thin sheet as crustal layer to investigate the evolution of distributed ductile strain in FTBs. Here, we tested the role of mechanical coupling at the basal decollement (i.e., weak versus strong) on the nature of ductile strain variations within a deforming tectonic wedge. Convergence velocity has been kept constant in all experiments to avoid the influence of rate-dependence on viscous rheology. Our results reveal that the mode of wedge growth with changing basal coupling is crucial for varying strain pattern towards the hinterland. Weak decollement models yield a zone of constriction towards the central part of the hinterland, explaining the occurrence of isolated patches of L-tectonites and cross-folds in FTBs; while strong decollement condition allows the gravity-driven flow to be dominant over horizontal shortening, leading to rotation of earlier structures and formation of orogen-parallel recumbent folds, particularly towards the hinterland. The deformation towards the frontal part of the tectonic wedge, irrespective of coupling strength in both models is similar, forming a characteristic pattern of pervasive, hinterland dipping ductile fabrics. We correlate our findings to infer that spatio-temporal variations in basal coupling are responsible for the development of variably occurring ductile structures in FTBs.</p>
<p>The outer wedge of the Indo-Burma wedge (IBW) has resulted due to oblique subduction of the Indian Plate below the Burma. In this study, we will use the analysis of outcrop-scale structures from Tripura-Mizoram fold belt (TMFB) to evaluate the structural evolution of the outer wedge of IBW. TMFB belongs to the widest section of the outer wedge that stretches from east to west for around 270 km (along 23.5&#176; N latitude). The first order structure of the outer wedge is characterized by a series of north-south trending anticlines-and-synclines of varying tightness. Analysis of our field observations provide a detailed understanding on the evolution of the first-order structure of the outer wedge of IBW. Weshow that the style of folding progressively becomes complex towards the hinterland direction of the wedge. The complexity of the fold structure is defined by the development of different geometries of folds, including refolding of earlier structures. Interestingly, different geometries of folds towards the hinterland share a uniform orientation of folds axes, implying pure shear deformation. Our field observations allow us to infer that the outer wedge sediments of IBW have deformed in a ductile manner over a shallow decollement, lying beneath the Neogene sediments of the outer wedge. We attribute the ductile behaviour of the outer wedge sediments to the dominance of weak shale horizons and high pore fluid pressure in the entire Neogene sequence of the outer wedge. To gain a complete understanding on the style of the strain distribution within TMFB, we performed scaled laboratory modelling under oblique convergence. We used Polydimethyl Siloxane (PDMS) to simulate the viscous rheology of the Neogene sediments. Model results show strong consistency not only with the existence of across-strike variations in the tightness of fold patterns from east to west but also provides a strong basis for explaining the occurrence of along-strike variations of deformation intensity in the outer wedge of IBW, which gradually increases southward with narrowing the width of the wedge.</p>
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.
hi@scite.ai
10624 S. Eastern Ave., Ste. A-614
Henderson, NV 89052, USA
Copyright © 2024 scite LLC. All rights reserved.
Made with 💙 for researchers
Part of the Research Solutions Family.