scholarly journals Nucleobindin-1 regulates ECM degradation by promoting intra-Golgi trafficking of MMPs

2020 ◽  
Vol 219 (8) ◽  
Author(s):  
Natalia Pacheco-Fernandez ◽  
Mehrshad Pakdel ◽  
Birgit Blank ◽  
Ismael Sanchez-Gonzalez ◽  
Kathrin Weber ◽  
...  
Keyword(s):  
Cell Migration ◽  
Matrix Metalloproteinases ◽  
Golgi Apparatus ◽  
Cell Invasion ◽  
Ecm Remodeling ◽  
Human Macrophages ◽  
Tissue Organization ◽  
Health And Disease ◽  
Ecm Degradation ◽  
Golgi Protein

Matrix metalloproteinases (MMPs) degrade several ECM components and are crucial modulators of cell invasion and tissue organization. Although much has been reported about their function in remodeling ECM in health and disease, their trafficking across the Golgi apparatus remains poorly understood. Here we report that the cis-Golgi protein nucleobindin-1 (NUCB1) is critical for MMP2 and MT1-MMP trafficking along the Golgi apparatus. This process is Ca2+-dependent and is required for invasive MDA-MB-231 cell migration as well as for gelatin degradation in primary human macrophages. Our findings emphasize the importance of NUCB1 as an essential component of MMP transport and its overall impact on ECM remodeling.

Role of Matrix Metalloproteinases in Degenerative Kidney Disorders

2018 ◽  
Vol 25 (15) ◽  
pp. 1805-1816 ◽  
Author(s):  
Shifa Narula ◽  
Chanderdeep Tandon ◽  
Simran Tandon
Keyword(s):  
Matrix Metalloproteinases ◽  
Transforming Growth Factor ◽  
Kidney Diseases ◽  
Transforming Growth Factor Β1 ◽  
Bioactive Molecules ◽  
Tissue Inhibitors Of Metalloproteinases ◽  
Ecm Remodeling ◽  
Surface Receptors ◽  
Calcium Dependent ◽  
Ecm Degradation

Matrix metalloproteinases (MMPs) are members of calcium dependent-zinc containing endopeptidases that play a pivotal role in extracellular matrix (ECM) remodeling. MMPs are also known to cleave non-matrix proteins, including cell surface receptors, TNF-α, angiotensin-II, growth factors, (especially transforming growth factor-β1, ΤGF- β1) plasminogen, endothelin and other bioactive molecules. The tissue inhibitors of metalloproteinases (TIMPs) inhibit the activity of MMPs and decrease ECM degradation. Various patho-physiological conditions have been linked with the imbalance of ECM synthesis and degradation. Numerous studies have reported the significance of MMPs and TIMPs in the progression of kidney pathologies, including glomerulonephritis, diabetic nephropathy, renal cancer, and nephrolithiasis. Although dysregulated activity of MMPs could directly or indirectly lead to pathological morbidities, their contribution in disease progression is still understated. Specifically, MMP activity in the kidneys and it's relation to kidney diseases has been the subject of a limited number of investigations. Therefore, the aim of the present review is to provide an updated insight of the involvement of MMPs and TIMPs in the pathogenesis of inflammatory and degenerative kidney disorders.

scholarly journals Matrix Metalloproteinases as Potential Biomarkers and Therapeutic Targets in Liver Diseases

Cells ◽  
2020 ◽  
Vol 9 (5) ◽  
pp. 1212 ◽  
Author(s):  
Eline Geervliet ◽  
Ruchi Bansal
Keyword(s):  
Matrix Metalloproteinases ◽  
Liver Diseases ◽  
Current Knowledge ◽  
Expression Patterns ◽  
Therapeutic Targets ◽  
Scar Tissue ◽  
Therapeutic Drug ◽  
Ecm Remodeling ◽  
Ecm Degradation ◽  
End Stage

Chronic liver diseases, characterized by an excessive accumulation of extracellular matrix (ECM) resulting in scar tissue formation, are a growing health problem causing increasing morbidity and mortality worldwide. Currently, therapeutic options for tissue fibrosis are severely limited, and organ transplantation is the only treatment for the end-stage liver diseases. During liver damage, injured hepatocytes release proinflammatory factors resulting in the recruitment and activation of immune cells that activate quiescent hepatic stellate cells (HSCs). Upon activation, HSCs transdifferentiate into highly proliferative, migratory, contractile and ECM-producing myofibroblasts. The disrupted balance between ECM deposition and degradation leads to the formation of scar tissue referred to as fibrosis. This balance can be restored either by reducing ECM deposition (by inhibition of HSCs activation and proliferation) or enhancing ECM degradation (by increased expression of matrix metalloproteinases (MMPs)). MMPs play an important role in ECM remodeling and represent an interesting target for therapeutic drug discovery. In this review, we present the current knowledge about ECM remodeling and role of the different MMPs in liver diseases. MMP expression patterns in different stages of liver diseases have also been reviewed to determine their role as biomarkers. Finally, we highlight MMPs as promising therapeutic targets for the resolution of liver diseases.

scholarly journals Membrane-type matrix metalloproteinases mediate curcumin-induced cell migration in non-tumorigenic colon epithelial cells differing in Apc genotype

2002 ◽  
Vol 23 (6) ◽  
pp. 1065-1070 ◽  
Author(s):  
Jenifer I. Fenton ◽  
Margaret S. Wolff ◽  
Michael W. Orth ◽  
Norman G. Hord
Keyword(s):  
Cell Migration ◽  
Epithelial Cells ◽  
Matrix Metalloproteinases ◽  
Membrane Type

scholarly journals STIM1- and Orai1-mediated Ca2+ oscillation orchestrates invadopodium formation and melanoma invasion

2014 ◽  
Vol 207 (4) ◽  
pp. 535-548 ◽  
Author(s):  
Jianwei Sun ◽  
Fujian Lu ◽  
Huifang He ◽  
Junling Shen ◽  
Jane Messina ◽  
...  
Keyword(s):  
Extracellular Matrix ◽  
Plasma Membrane ◽  
Mouse Model ◽  
Matrix Metalloproteinase ◽  
Cell Invasion ◽  
Cancer Cell Invasion ◽  
Invasion And Metastasis ◽  
Melanoma Invasion ◽  
Ecm Degradation ◽  
Underlying Mechanisms

Ca2+ signaling has been increasingly implicated in cancer invasion and metastasis, and yet, the underlying mechanisms remained largely unknown. In this paper, we report that STIM1- and Orai1-mediated Ca2+ oscillations promote melanoma invasion by orchestrating invadopodium assembly and extracellular matrix (ECM) degradation. Ca2+ oscillation signals facilitate invadopodial precursor assembly by activating Src. Disruption of Ca2+ oscillations inhibited invadopodium assembly. Furthermore, STIM1 and Orai1 regulate the proteolysis activity of individual invadopodia. Mechanistically, Orai1 blockade inhibited the recycling of MT1–matrix metalloproteinase (MMP) to the plasma membrane and entrapped MT1-MMP in the endocytic compartment to inhibit ECM degradation. STIM1 knockdown significantly inhibited melanoma lung metastasis in a xenograft mouse model, implicating the importance of this pathway in metastatic dissemination. Our findings provide a novel mechanism for Ca2+-mediated cancer cell invasion and shed new light on the spatiotemporal organization of store-operated Ca2+ signals during melanoma invasion and metastasis.

Phosphatidylinositol 4-Phosphate in the Golgi Apparatus Regulates Cell–Cell Adhesion and Invasive Cell Migration in Human Breast Cancer

2014 ◽  
Vol 74 (11) ◽  
pp. 3054-3066 ◽  
Author(s):  
Emi Tokuda ◽  
Toshiki Itoh ◽  
Junya Hasegawa ◽  
Takeshi Ijuin ◽  
Yukiko Takeuchi ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cell Migration ◽  
Cell Adhesion ◽  
Golgi Apparatus ◽  
Human Breast Cancer ◽  
Human Breast ◽  
Phosphatidylinositol 4 ◽  
Invasive Cell ◽  
Cell Cell

Dimethylfumarate inhibits tumor cell invasion and metastasis by suppressing the expression and activities of matrix metalloproteinases in melanoma cells

2009 ◽  
Vol 33 (10) ◽  
pp. 1087-1094 ◽  
Author(s):  
Yuzuru Yamazoe ◽  
Masanobu Tsubaki ◽  
Hiroshi Matsuoka ◽  
Takao Satou ◽  
Tatsuki Itoh ◽  
...  
Keyword(s):  
Matrix Metalloproteinases ◽  
Tumor Cell ◽  
Cell Invasion ◽  
Melanoma Cells ◽  
Tumor Cell Invasion ◽  
Invasion And Metastasis

An electrospun poly(ε-caprolactone) scaffold modified with matrix metalloproteinase for cellularization and vascularization

2018 ◽  
Vol 6 (18) ◽  
pp. 2795-2802 ◽  
Author(s):  
Li Jiang ◽  
Jingchen Gao ◽  
Dongmin Song ◽  
Mingqiang Qiao ◽  
Di Tang ◽  
...  
Keyword(s):  
Cell Migration ◽  
Matrix Metalloproteinase ◽  
Promote Cell Migration ◽  
Ecm Degradation

HFBI-coated PCL scaffold modified with collagenase to promote cell migration though ECM degradation.

Abstract 1042: Viral Chemokine Modulating Protein, M-T7, Interrupts Chemokine : Glycosaminoglycan (GAG) Interaction: M-T7 Inhibitory Activity is Dependent upon Y46 and V210 aminoacid residues

Circulation ◽  
2007 ◽  
Vol 116 (suppl_16) ◽  
Author(s):  
Erbin Dai ◽  
Dana McIvor ◽  
Liying Liu ◽  
Ganesh Munaswamy-Ramanujam ◽  
Yunming Sun ◽  
...  
Keyword(s):  
Cell Migration ◽  
Cell Invasion ◽  
Inhibitory Activity ◽  
Active Sites ◽  
Point Mutations ◽  
List Type ◽  
Wild Type ◽  
Monocyte Activation ◽  
Cc Chemokine ◽  
Plaque Growth

Background: Chemokines bind to glycosaminoglycans (GAGs) forming gradients that direct inflammatory cell invasion. The viral chemokine modulating protein (CMP), MT-7 binds the C terminal, GAG-binding domain of chemokines and has been previously reported to significantly reduce cell invasion and plaque growth in rat aortic and renal transplant models. Two other viral CMPs, M-T1 and M3 CMPs bind the N terminal domain of chemokines that bind to cell surface receptors. To determine the role of CC chemokine receptor 2 (CCR2) and GAGs for M-T7 anti-inflammatory activity, effects of M-T7 on plaque growth were assessed after mouse CCR2 deficient (CCR2−/−) or GAG deficient (NDST1−/−) aortic allograft transplant. Mononuclear cell migration in response to MCP-1 or RANTES into mouse ascites was also tested. Active sites necessary for M-T7 inhibition of chemokine function and monocyte activation, were assessed by infusion of in the mouse cell migration and human monocyte membrane fluidity assays. Results: M-T7 significantly reduced cell migration and intimal hyperplasia in wild type CCR2+/+ (p<0.009), and CCR2−/− aortic transplants (p<0.026). M-T1 and M3 inhibited cell invasion and plaque in CCR2+/+, but not CCR2−/− mice. M-T7 inhibited plaque growth and CC chemokine (MCP-1 and RANTES)-induced cell migration in wild type mice (P<0.01), but not in NDST1−/− mice (P=0.34). Selected M-T7 point mutations Ty (Y)46A, and Val (V) 210A no longer block chemokine-induced cell migration nor monocyte activation, whereas Asn (N) 40, Asn (N) 63 and Val (V)129 retain inhibitory activity. Conclusions: M-T7 but not M-T1 nor M3, blocks cell migration and plaque growth in CCR2 deficient (CCR2−/−) mouse aortic transplant models. M-T7 loses the ability to block cell migration and plaque growth in NDST1−/−, GAG (heparan sulfate) deficient mice. Point mutations Tyr46 and Val 210 lack inflammatory for mouse and human inflammatory monocyte responses indicating that these amino acid residues on the M-T7 CMP protein are required for inhibitory activity.

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