scholarly journals mTOR repression in response to amino acid starvation promotes ECM degradation through MT1-MMP endocytosis arrest

2021 ◽  
Author(s):  
Cecilia Colombero ◽  
David Remy ◽  
Sandra Antoine ◽  
Anne-Sophie Macé ◽  
Pedro Monteiro ◽  
...  
Keyword(s):  
Amino Acid ◽  
Tumor Invasion ◽  
Pancreatic Tumor ◽  
Pericellular Matrix ◽  
Matrix Degradation ◽  
Coated Pits ◽  
Nutrient Sources ◽  
Growth Factor Deprivation ◽  
Order Of Magnitude ◽  
Ecm Degradation

AbstractUnder conditions of starvation, normal and tumor epithelial cells can rewire their metabolism towards the consumption of extracellular matrix-derived components as nutrient sources. The mechanism of pericellular matrix degradation by starved cells has been largely overlooked. Here we show that matrix degradation by breast and pancreatic tumor cells and patient-derived xenograft explants increases by one order of magnitude upon amino acid and growth factor deprivation. In addition, we found that collagenolysis requires the invadopodia components, TKS5 and the transmembrane metalloproteinase, MT1-MMP, which are key to the tumor invasion program. Increased collagenolysis is controlled by mTOR repression upon nutrient depletion or pharmacological inhibition by rapamycin. Our results reveal that starvation hampers clathrin-mediated endocytosis, resulting in MT1-MMP accumulation in arrested clathrin-coated pits. Our study uncovers a new mechanism whereby mTOR repression in starved cells leads to the repurposing of abundant plasma membrane clathrin-coated pits into robust ECM-degradative assemblies.

Comparison of the Potency of 8-L-Arginine, 8-D-Arginine and 8-D-Homoarginine Vasopressin Analogs with Substituted Phenylalanine in Position 2

1994 ◽  
Vol 59 (6) ◽  
pp. 1439-1450 ◽  
Author(s):  
Miroslava Žertová ◽  
Jiřina Slaninová ◽  
Zdenko Procházka
Keyword(s):  
Amino Acid ◽  
Solid Phase Synthesis ◽  
Solid Phase ◽  
Basic Amino Acid ◽  
The Other ◽  
Side Chain ◽  
Inhibitory Potency ◽  
Phase Synthesis ◽  
Other Hand ◽  
Order Of Magnitude

An analysis of the uterotonic potencies of all analogs having substituted L- or D-tyrosine or -phenylalanine in position 2 and L-arginine, D-arginine or D-homoarginine in position 8 was made. The series of analogs already published was completed by the solid phase synthesis of ten new analogs having L- or D-Phe, L- or D-Phe(2-Et), L- or D-Phe(2,4,6-triMe) or D-Tyr(Me) in position 2 and either L- or D-arginine in position 8. All newly synthesized analogs were found to be uterotonic inhibitors. Deamination increases both the agonistic and antagonistic potency. In the case of phenylalanine analogs the change of configuration from L to D in position 2 enhances the uterotonic inhibition for more than 1 order of magnitude. The L to D change in position 8 enhances the inhibitory potency negligibly. Prolongation of the side chain of the D-basic amino acid in position 8 seems to decrease slightly the inhibitory potency if there is L-substituted amino acid in position 2. On the other hand there is a tendency to the increase of the inhibitory potency if there is D-substituted amino acid in position 2.

Inhibition of tumor invasion and extracellular matrix degradation by ubenimex (bestatin)

1992 ◽  
Vol 10 (1) ◽  
pp. 49-59 ◽  
Author(s):  
Junya Yoneda ◽  
Ikuo Saiki ◽  
Hideji Fujii ◽  
Fuminori Abe ◽  
Yutaka Kojima ◽  
...  
Keyword(s):  
Extracellular Matrix ◽  
Tumor Invasion ◽  
Matrix Degradation ◽  
Extracellular Matrix Degradation

scholarly journals Non-Concordance of Radiocarbon and Amino Acid Racemization Deduced Age Estimates on Human Bone

Radiocarbon ◽  
1983 ◽  
Vol 25 (2) ◽  
pp. 647-654 ◽  
Author(s):  
R E Taylor
Keyword(s):  
Amino Acid ◽  
Aspartic Acid ◽  
Human Bone ◽  
Amino Acid Racemization ◽  
Aspartic Acid Racemization ◽  
Order Of Magnitude ◽  
Direct Counting ◽  
Organic Fractions ◽  
Skeletal Samples ◽  
Age Estimates

Radiocarbon determinations, employing both decay and direct counting, were obtained on various organic fractions of four human skeletal samples previously assigned ages ranging from 28,000 to 70,000 years on the basis of their D/L aspartic acid racemization values. In all four cases, the 14C values require an order of magnitude reduction in age.

scholarly journals Complementary techniques to analyse pericellular matrix formation by human MSC within hyaluronic acid hydrogels

2020 ◽  
Vol 1 (8) ◽  
pp. 2888-2896
Author(s):  
Christoph Salzlechner ◽  
Anders Runge Walther ◽  
Sophie Schell ◽  
Nicholas Groth Merrild ◽  
Tabasom Haghighi ◽  
...  
Keyword(s):  
Hyaluronic Acid ◽  
Amino Acid ◽  
Cell Encapsulation ◽  
Pericellular Matrix ◽  
Encapsulated Cells ◽  
The Matrix ◽  
Canonical Amino Acid ◽  
Confocal Raman ◽  
Complementary Techniques ◽  
Raman Spectral

Hydrogels are used widely for cell encapsulation to mimic the native ECM. Here, we characterise and visualise the matrix secreted by encapsulated cells by combining fluorescent non-canonical amino acid tagging with confocal Raman spectral imaging.

Is leucine an allosteric modulator of the lysine transporter in the intestinal basolateral membrane?

1987 ◽  
Vol 253 (5) ◽  
pp. G637-G642 ◽  
Author(s):  
K. Lawless ◽  
D. Maenz ◽  
C. Cheeseman
Keyword(s):  
Amino Acid ◽  
Basolateral Membrane ◽  
Membrane Vesicles ◽  
Transport Systems ◽  
Low Concentrations ◽  
Carrier Mediated Transport ◽  
Order Of Magnitude ◽  
Dibasic Amino Acid ◽  
Voltage Clamping ◽  
Stimulation Of

The transport of the dibasic amino acid L-lysine was investigated using basolateral membrane vesicles prepared from rat jejunal mucosal scrapings. The majority of the carrier-mediated transport was unaffected by the presence of sodium in the incubation medium, but voltage clamping of the vesicles did increase lysine uptake, indicating an associated movement of charge. Kinetic analysis of lysine influx and efflux showed the system to be symmetrical, but although the Vmax was comparable to other amino acid transport systems in this membrane, the dissociation constant for the overall reaction (KT) was an order of magnitude larger. This low affinity for lysine would explain the relatively slow rate of transport of this amino acid across the basolateral membrane. Competition experiments indicated that this system has a relatively narrow specificity carrying only lysine, arginine, ornithine, and histidine. In contrast the presence of L-leucine caused a marked stimulation of lysine efflux and influx across the vesicles. This effect was observed with leucine concentrations as low as 0.1 microM. It is concluded that although the lysine transport system in the basolateral membrane is slow in its basal state it can be rapidly turned on by the presence of L-leucine. The remarkably low concentrations required to do this suggest a possible allosteric interaction between the transporter and this neutral amino acid.

scholarly journals On the chemical diversity of the prebiotic ocean of early Earth

2014 ◽  
Vol 14 (3) ◽  
pp. 497-504
Author(s):  
Carlo Canepa
Keyword(s):  
Amino Acid ◽  
Average Length ◽  
Chemical Species ◽  
Catalytic Efficiency ◽  
Chemical Diversity ◽  
Aqueous Environment ◽  
Amino Acid Residues ◽  
Catalytically Active ◽  
Order Of Magnitude ◽  
The Mean

AbstractThis work investigates the consequences on the diverse number of chemical species in a pre-biotic terrestrial aqueous environment endowed with an amino acid source induced by the spontaneous build-up of catalytically active polypeptides from amino acid monomers. The assumed probability that a randomly formed polypeptide exhibits catalytic properties is dependent on constraining both the chemical identity and the position of a fraction of the amino acid residues. Within this hypothesis, and using values of the average length n of the catalytic polypeptides about one half of the present-day enzymes, the stationary-state concentration of the catalytically active polypeptides is ≈10−30 −10−19 M, and the ratio of the concentration of a product of a catalytic process to the initial concentration of the corresponding substrate is predicted to be ≈10−6−105. Matching the mean life of each catalytic polypeptide to the mean life of its substrate (λ ≈ ω) is only possible by significantly raising the intensity of the source of the amino acid monomers. Under these hypothetical optimal conditions, the mean lives of the catalytic polypeptides and their substrates have values ω−1 ≈ λ−1 ≈10 yr and the asymptotic concentration of each product is of the same order of magnitude as the concentration of the substrate. In all cases the catalytic efficiency necessary to form the active peptides takes the typical values of present-day enzymes.

scholarly journals A single amino acid change in the cytoplasmic domain alters the polarized delivery of influenza virus hemagglutinin.

1991 ◽  
Vol 114 (3) ◽  
pp. 413-421 ◽  
Author(s):  
C B Brewer ◽  
M G Roth
Keyword(s):  
Influenza Virus ◽  
Amino Acid ◽  
Amino Acid Change ◽  
Mdck Cells ◽  
Single Amino Acid ◽  
Apical Surface ◽  
Membrane Glycoproteins ◽  
Coated Pits ◽  
Influenza Virus Hemagglutinin ◽  
Single Amino Acid Change

In the polarized kidney cell line MDCK, the influenza virus hemagglutinin (HA) has been well characterized as a model for apically sorted membrane glycoproteins. Previous work from our laboratory has shown that a single amino acid change in the cytoplasmic sequence of HA converts it from a protein that is excluded from coated pits to one that is efficiently internalized. Using trypsin or antibodies to mark protein on the surface, we have shown in MDCK cells that HA containing this mutation is no longer transported to the apical surface but instead is delivered directly to the basolateral plasma membrane. We propose that a cytoplasmic feature similar to an endocytosis signal can cause exclusive basolateral delivery.

scholarly journals Synergistic metalloproteinase-based remodeling of matrix by pancreatic tumor and stromal cells

PLoS ONE ◽  
2021 ◽  
Vol 16 (3) ◽  
pp. e0248111
Author(s):  
Hong Cao ◽  
Li Qiang ◽  
Jing Chen ◽  
Katherine M. Johnson ◽  
Mark A. McNiven ◽  
...  
Keyword(s):  
Tumor Cells ◽  
Stromal Cells ◽  
Pancreatic Tumor ◽  
Tumor Cell Invasion ◽  
Matrix Remodeling ◽  
Stromal Fibroblasts ◽  
Peripheral Tissues ◽  
Ecm Remodeling ◽  
Ecm Degradation ◽  
Cell Medium

The process by which tumor cells mechanically invade through the surrounding stroma into peripheral tissues is an essential component of metastatic dissemination. Matrix metalloproteinase (MMP)-mediated extracellular matrix (ECM) degradation plays an important role in this invasive process. Defining the contribution and interaction between these MMPs during invasion remains a key interest in the development of targeted anti-metastatic therapies. In this study we have utilized multiple different stromal fibroblasts and tumor cells to define the relative contributions between cancer cells and stromal cells during MMP-dependent matrix remodeling and pancreatic (PDAC) tumor cell invasion. We find that tumor cells co-cultured with the conditioned medium from stromal fibroblasts exhibited a substantial increase in invadopodial-based matrix degradation and transwell invasion. This increase is dependent on pro-MMP2 expressed and secreted by stromal fibroblasts. Further, the pro-MMP2 from the stromal fibroblasts is activated by MT1-MMP expressed on the tumor cells. Depletion of MT1-MMP, the known activator of MMP2, in tumor cells largely blocked matrix remodeling, even in the presence of stromal cell medium. In summary, these findings implicate an important interplay between MT1-MMP from tumor cells and MMP2 from fibroblasts as a key component for ECM remodeling and invasion.

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