Low molecular weight heparin inhibits melanoma cell adhesion and migration through a PKCa/JNK signaling pathway inducing actin cytoskeleton changes

2011 ◽  
Vol 312 (2) ◽  
pp. 235-244 ◽  
Author(s):  
Georgia Chalkiadaki ◽  
Dragana Nikitovic ◽  
Pavlos Katonis ◽  
Aikaterini Berdiaki ◽  
Aristidis Tsatsakis ◽  
...  
2002 ◽  
Vol 302 (1) ◽  
pp. 290-295 ◽  
Author(s):  
Kent W. Christopherson ◽  
James J. Campbell ◽  
Jeffrey B. Travers ◽  
Robert A. Hromas

Blood ◽  
2002 ◽  
Vol 99 (7) ◽  
pp. 2351-2359 ◽  
Author(s):  
Wen-Mei Yu ◽  
Teresa S. Hawley ◽  
Robert G. Hawley ◽  
Cheng-Kui Qu

Gab2, a newly identified pleckstrin homology domain-containing docking protein, is a major binding protein of SHP-2 tyrosine phosphatase in interleukin (IL)-3–stimulated hematopoietic cells. Its signaling mechanism remains largely unknown. We report here an important regulatory role for Gab2 in β1 integrin signaling pathway that mediates hematopoietic cell adhesion and migration. Cross-linking of the β1 integrin on Ba/F3 cells induced rapid tyrosine phosphorylation of Gab2 and its association with Syk kinase, SHP-2 phosphatase, and the p85 subunit of phosphatidylinositol (PI)-3 kinase. In addition, Gab2 was also constitutively associated with SHP-1 phosphatase via its C-terminal Src homology 2 domain. Overexpression of the pleckstrin homology domain or a mutant Gab2 molecule lacking SHP-2 binding sites resulted in significant reductions in Ba/F3 cell adhesion and migration. Biochemical analyses revealed that enforced expression of Gab2 mutant molecules dramatically reduced β1-integrin ligation-triggered PI3 kinase activation, whereas Erk kinase activation remained unaltered. Furthermore, transduction of primary hematopoietic progenitor cells from viable motheaten mice with these mutant Gab2 molecules also significantly ameliorated their enhanced migration capacity associated with theSHP1 gene mutation. Taken together, these results suggest an important signaling role for Gab2 in regulating hematopoietic cell adhesion and migration.


2011 ◽  
Vol 2 (2) ◽  
pp. 363-367 ◽  
Author(s):  
CAMILLE ETTELAIE ◽  
DONNA FOUNTAIN ◽  
MARY ELIZABETH W. COLLIER ◽  
ELLIE BEEBY ◽  
YU PEI XIAO ◽  
...  

2021 ◽  
Author(s):  
Chen Chen ◽  
◽  
Peng Chen ◽  
Xia Liu ◽  
Hua Li

Review question / Objective: The aim of this meta-analysis is to evaluate the efficacy and safety of intraoperative infusion of combined 5-fluorouracil and low molecular weight heparin (LMWH) for the prevention of postoperative proliferative vitreoretinopathy in patients with retinal detachment. Condition being studied: Postoperative proliferative vitreoretinopathy (PVR) is the primary cause of failure of retinal reattachment surgery. 5-fluorouracil (5-FU) inhibits the proliferation of fibroblasts, and suppresses collagen contraction. On the other hand, heparin reduces fibrin exudation, and inhibits the adhesion and migration of retinal pigment epithelial cells. We conduct this comprehensive literature search and meta-analysis to address whether intraoperative infusion of combined 5-FU and LWMH improves the primary success rate of pars plana vitrectomy, as well as reduces postoperative PVR. Our study aims to provide clinical evidence for retinal surgeons concerning their choice of intraoperative medication.


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