Dataset Information

Oncosuppressive roles of decorin through regulation of multiple receptors and diverse signaling pathways.

ABSTRACT: Decorin is a stromal-derived prototype member of the small leucine-rich proteoglycan gene family. In addition to its functions as a regulator of collagen fibrillogenesis and TGF-β activity soluble decorin acts as a pan-receptor tyrosine kinase (RTK) inhibitor. Decorin binds to various RTKs including EGFR HER2 HGFR/Met VEGFR2 TLR and IGFR. Although the molecular mechanism for the action of decorin on these receptors is not entirely elucidated overall decorin evokes transient activation of these receptors with suppression of downstream signaling cascades culminating in growth inhibition followed by their physical downregulation via caveosomal internalization and degradation. In the case of Met decorin leads to decreased β-catenin signaling pathway and growth suppression. As most of these RTKs are responsible for providing a growth advantage to cancer cells the result of decorin treatment is oncosuppression. Another decorin-driven mechanism to restrict cancer growth and dissemination is by impeding angiogenesis via vascular endothelial growth factor receptor 2 (VEGFR2) and the concurrent activation of protracted endothelial cell autophagy. In this review we will dissect the multiple roles of decorin in cancer biology and its potential use as a next-generation protein-based adjuvant therapy to combat cancer.

SUBMITTER: Xie C

PROVIDER: S-EPMC8917911 | biostudies-literature | 2022 Mar

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Oncosuppressive roles of decorin through regulation of multiple receptors and diverse signaling pathways.

Xie Christopher C Mondal Dipon K DK Ulas Mikdat M Neill Thomas T Iozzo Renato V RV

American journal of physiology. Cell physiology 20220216 3

Decorin is a stromal-derived prototype member of the small leucine-rich proteoglycan gene family. In addition to its functions as a regulator of collagen fibrillogenesis and TGF-β activity soluble decorin acts as a pan-receptor tyrosine kinase (RTK) inhibitor. Decorin binds to various RTKs including EGFR HER2 HGFR/Met VEGFR2 TLR and IGFR. Although the molecular mechanism for the action of decorin on these receptors is not entirely elucidated overall decorin evokes transient activation of these r ...[more]

PMID: 35171698

Similar Datasets

Project description:Glycerol metabolism has been well studied biochemically. However, the means by which glycerol functions in plant development is not well understood. This study aimed to investigate the mechanism underlying the effects of glycerol on root development in Arabidopsis thaliana. Exogenous glycerol inhibited primary root growth and altered lateral root development in wild-type plants. These phenotypes appeared concurrently with increased endogenous glycerol-3-phosphate (G3P) and H2O2 contents in seedlings, and decreased phosphate levels in roots. Upon glycerol treatment, G3P level and root development did not change in glycerol kinase mutant gli1, but G3P level increased in gpdhc1 and fad-gpdh mutants, which resulted in more severely impaired root development. Overexpression of the FAD-GPDH gene attenuated the alterations in G3P, phosphate and H2O2 levels, leading to increased tolerance to exogenous glycerol, which suggested that FAD-GPDH plays an important role in modulating this response. Free indole-3-acetic acid (IAA) content increased by 46%, and DR5pro::GUS staining increased in the stele cells of the root meristem under glycerol treatment, suggesting that glycerol likely alters normal auxin distribution. Decreases in PIN1 and PIN7 expression, β-glucuronidase (GUS) staining in plants expressing PIN7pro::GUS and green fluorescent protein (GFP) fluorescence in plants expressing PIN7pro::PIN7-GFP were observed, indicating that polar auxin transport in the root was downregulated under glycerol treatment. Analyses with auxin-related mutants showed that TIR1 and ARF7 were involved in regulating root growth under glycerol treatment. Glycerol-treated plants showed significant reductions in root meristem size and cell number as revealed by CYCB1;1pro::GUS staining. Furthermore, the expression of CDKA and CYCB1 decreased significantly in treated plants compared with control plants, implying possible alterations in cell cycle progression. Our data demonstrated that glycerol treatment altered endogenous levels of G3P, phosphate and ROS, affected auxin distribution and cell division in the root meristem, and eventually resulted in modifications of root development.

Project description:We tested the hypothesis that simultaneous transgenic overexpression of a select quartet of growth factors activates diverse signaling pathways for mobilization and participation of various stem/progenitor cells for cardiogenesis in the infarcted heart. Human insulin growth factor-1 (IGF-1), vascular endothelial growth factor (VEGF), stromal cell-derived factor-1 (SDF-1a), and hepatocyte growth factor (HGF) plasmids were synthesized and transfected into skeletal myoblasts (SM) from young male wild-type or transgenic rats expressing green fluorescent protein (GFP). Overexpression of growth factors in transfected SM ((Trans)SM) was confirmed by reverse transcription polymerase chain reaction, western blotting, and fluorescence immunostaining. Using our custom-made growth factor array and western blotting, multiple angiogenic and prosurvival factors were detected in (Trans)SM, including secreted frizzled related protein-1,2,4,5, matrix metalloproteinases-3 and 9, connexin-43, netrin-1, Nos-2, Wnt-3, Akt, MAPK42/44, Stat3, nuclear factor kappa B (NFκB), hypoxia-inducible factor 1 (HIF-1α), and protein kinase C (PKC). The conditioned medium (CM) from (Trans)SM was cytoprotective for cardiomyocytes following H(2)O(2) treatment [P<0.01 vs. CM from native SM ((Nat)SM)], promoted a higher transwell migration of human umbilical cord vein endothelial cells (223.3±1.8, P<0.01) and in vitro tube formation (47.8±1.9, P<0.01). Intramyocardial transplantation of 1.5×10(6) (Trans)SM (group-3) in a rat model of acute myocardial infarction induced extensive mobilization of cMet(+), ckit(+), ckit(+)/GATA(4+), CXCR4(+), CD44(+), CD31(+), and CD59(+) cells into the infarcted heart on day 7 and improved integration of (Trans)SM in the heart compared to (Nat)SM (group 2) (P<0.05). Extensive neomyogenesis and angiogenesis in group-3 (P<0.01 vs. group-2), with resultant attenuation of infarct size (P<0.01 vs. group-2) and improvement in global heart function (P<0.01 vs. group-2) was observed at 8 weeks. In conclusion, simultaneous activation of diverse signaling pathways by overexpression of multiple growth factors caused massive mobilization and homing of stem/progenitor cells from peripheral circulation, the bone marrow, and the heart for accelerated repair of the infarcted myocardium.

Dataset Information

Oncosuppressive roles of decorin through regulation of multiple receptors and diverse signaling pathways.

Publications

Oncosuppressive roles of decorin through regulation of multiple receptors and diverse signaling pathways.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets