Regulation of S100A10 by the PML-RAR-α oncoprotein

O’Connell, Paul A.; Madureira, Patrícia A.; Berman, Jason N.; Liwski, Robert; Waisman, David M.

doi:10.1182/blood-2010-07-298851

Cited by 64 publications

(87 citation statements)

References 36 publications

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“…34 Shortly after these reports, another group demonstrated the presence of S100A10 on the surface of endothelial cells and the reversible interaction of the C-terminal lysine of S100A10 with both tPA and plasminogen. 35,36 This group established that S100A10 was present in a heterotetrameric complex with ANXA2 on the surface of many cells 35,[37][38][39][40][41] and demonstrated that purified AIIt bound tPA and plasminogen via the C-terminal lysine of the S100A10 subunit without the participation of the ANXA2 subunit. 36,42,43 With the development of methods to deplete cells of ANXA2 and the report of defective fibrinolysis in the ANXA2 knockout mouse, 44 it appeared that ANXA2 might play a role in cellular fibrinolysis.…”

Section: Historical Perspectivementioning

confidence: 99%

“…However, subsequent studies demonstrated that depletion of ANXA2 resulted in the concomitant depletion of S100A10, 45 and multiple other reports demonstrated that the proposed cleaved form of ANXA2 was undetectable in several cellular model systems of fibrinolysis. [37][38][39][40][41] Thus, it became apparent that the extracellular function of ANXA2 was most likely to transport and localize the plasminogen regulatory protein S100A10 to the cell surface. To this end, it was demonstrated that the phosphorylation of ANXA2 regulated its translocation to the extracellular surface.…”

Section: Historical Perspectivementioning

confidence: 99%

“…40 APL is a special subtype of acute myeloid leukemia whose biologic and clinical features include the presence of the specific t(15;17) chromosomal translocation in leukemic blasts and the frequent existence of severe hemorrhagic diathesis at the time of diagnosis. [106][107][108] The mechanism for the hemorrhagic deaths partially involves hyperfibrinolysis, which occurs because of the excessive production of plasmin at the surface of the promyelocytic leukemic cells.…”

Section: The Role Of S100a10 In Diseasementioning

confidence: 99%

“…109 We observed that depletion of S100A10 from the APL cell line, NB4, which constitutively expresses the PML-RAR-␣ oncoprotein, resulted in a 70% loss in plasminogen binding and a 64% loss in plasmin generation by the NB4 cells. 40 In addition to measuring plasmin generation, we also examined the ability of NB4 cells to migrate through a fibrin barrier as an independent measure of fibrinolytic activity of the cells. We observed that depletion of S100A10 resulted in 60% fewer NB4 cells migrating through the fibrin barrier.…”

Section: The Role Of S100a10 In Diseasementioning

confidence: 99%

“…41 Analysis of cell surface ANXA2 has identified intact ANXA2 but failed to observe any truncated ANXA2. 37,39,40 Recently, we examined the molecular weight forms of ANXA2 at the endothelial cell surface by Western blotting. 41 Although native ANXA2 was easily detected, we were unable to detect any lower molecular weight (truncated) forms of ANXA2.…”

Section: The Role Of Anxa2 In Fibrinolysismentioning

confidence: 99%

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The role of the annexin A2 heterotetramer in vascular fibrinolysis

Madureira¹,

Surette²,

Phipps³

et al. 2011

Blood

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110

129

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The vascular endothelial cells line the inner surface of blood vessels and function to maintain blood fluidity by producing the protease plasmin that removes blood clots from the vasculature, a process called fibrinolysis. Plasminogen receptors play a central role in the regulation of plasmin activity. The protein complex annexin A2 heterotetramer (AIIt) is an important plasminogen receptor at the surface of the endothelial cell. AIIt is composed of 2 molecules of annexin A2 (ANXA2) bound together by a dimer of the protein S100A10. Recent work performed by our laboratory allowed us to clarify the specific roles played by ANXA2 and S100A10 subunits within the AIIt complex, which has been the subject of debate for many years. The ANXA2 subunit of AIIt functions to stabilize and anchor S100A10 to the plasma membrane, whereas the S100A10 subunit initiates the fibrinolytic cascade by colocalizing with the urokinase type plasminogen activator and receptor complex and also providing a common binding site for both tissue-type plasminogen activator and plasminogen via its C-terminal lysine residue. The AIIt mediated colocalization of the plasminogen activators with plasminogen results in the rapid and localized generation of plasmin to the endothelial cell surface, thereby regulating fibrinolysis. (Blood. 2011;118(18):4789-4797) IntroductionThe vascular endothelium consists of a single cell layer lining all vessels that separates the blood from the tissues. It is estimated to be composed of ϳ 10 13 cells, representing a weight of 1.5 kg and an area of 4000 to 7000 m 2 . 1 Endothelial cells play a role in primary hemostasis, coagulation, fibrinolysis, and regulation of vasomotor tone. In addition to regulating the flow of nutrients, the vascular endothelium regulates many diverse biologically active molecules. These functions of the endothelium are achieved through the presence of membrane-bound receptors for various proteins, lipidtransporting complexes, hormones, and metabolites, as well as through specific extracellular proteins and receptors that regulate cell-cell and cell-matrix interactions. 2 Whereas exposure to inflammatory and/or septic stimuli rapidly leads to procoagulant behavior, unperturbed endothelial cells provide an anticoagulant environment. After vascular insult, endothelial cells express tissue factor and initiate the coagulation cascade that results in thrombin activation and fibrin clot deposition. At the same time, anticoagulant pathways and fibrinolysis are activated to avoid disseminated coagulation and to also limit fibrin accumulation. [3][4][5] Fibrinogen is a large glycoprotein that constitutes the main component of a fibrin clot. Each fibrinogen molecule is composed of 2 sets of A␣-, B␤-, and ␥-polypeptide chains that form a protein containing 2 distal D regions connected to a central E region by a coiled-coil segment. 6 Fibrin is produced on cleavage of the fibrinopeptides by thrombin, which results in the formation of double-stranded half-staggered oligomers that lengthen into protofibrils...

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Section: Historical Perspectivementioning

confidence: 99%

Section: Historical Perspectivementioning

confidence: 99%

Section: The Role Of S100a10 In Diseasementioning

confidence: 99%

Section: The Role Of S100a10 In Diseasementioning

confidence: 99%

Section: The Role Of Anxa2 In Fibrinolysismentioning

confidence: 99%

See 3 more Smart Citations

The role of the annexin A2 heterotetramer in vascular fibrinolysis

Madureira¹,

Surette²,

Phipps³

et al. 2011

Blood

Self Cite

110

129

View full text Add to dashboard Cite

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S100A10, a novel biomarker in pancreatic ductal adenocarcinoma

et al. 2018

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Pancreatic cancer is arguably the deadliest cancer type. The efficacy of current therapies is often hindered by the inability to predict patient outcome. As such, the development of tools for early detection and risk prediction is key for improving outcome and quality of life. Here, we introduce the plasminogen receptor S100A10 as a novel predictive biomarker and a driver of pancreatic tumor growth and invasion. We demonstrated that S100A10 mRNA and protein are overexpressed in human pancreatic tumors compared to normal ducts and nonductal stroma. S100A10 mRNA and methylation status were predictive of overall survival and recurrence‐free survival across multiple patient cohorts. S100A10 expression was driven by promoter methylation and the oncogene KRAS. S100A10 knockdown reduced surface plasminogen activation, invasiveness, and in vivo growth of pancreatic cancer cell lines. These findings delineate the clinical and functional contribution of S100A10 as a biomarker in pancreatic cancer.

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Acute myeloid leukemia commentary

Arceci

2013

Evidence‐Based Pediatric Oncology

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Regulation of S100A10 by the PML-RAR-α oncoprotein

Cited by 64 publications

References 36 publications

The role of the annexin A2 heterotetramer in vascular fibrinolysis

The role of the annexin A2 heterotetramer in vascular fibrinolysis

S100A10, a novel biomarker in pancreatic ductal adenocarcinoma

Acute myeloid leukemia commentary

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