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| 1 | Wnt signaling and Loxl2 promote aggressive osteosarcoma显示文摘Osteosarcoma(OS)is the most frequent primary malignant bone tumor in urgent need of better therapies.Using genetically modified mouse models(GEMMs),we demonstrate that Wnt signaling promotes c-Fos-induced OS formation via the actions of the collagen-modifying enzyme Loxl2.c-Fos/AP-1 directly regulates the expression of the Wnt ligands Wnt7b and Wnt9a in OS cells through promoter binding,and Wnt7b and Wnt9a in turn promote Loxl2 expression in murine and human OS cells through the transcription factors Zeb1 and Zeb2.Concordantly,inhibition of Wnt ligand secretion by inactivating the Wnt-less(Wls)gene in osteoblasts in c-Fos GEMMs either early or in a therapeutic setting reduces Loxl2 expression and progression of OS.Wls-deficient osteosarcomas proliferate less,are less mineralized and are enriched in fibroblastic cells surrounded by collagen fibers.Importantly,Loxl2 inhibition using either the pan-Lox inhibitor BAPN or a specific inducible shRNA reduces OS cell proliferation in vitro and decreases tumor growth and lung colonization in murine and human orthotopic OS transplantation models.Finally,OS development is delayed in c-Fos GEMMs treated with BAPN or with specific Loxl2 blocking antibodies.Congruently,a strong correlation between c-FOS,LOXL2 and WNT7B/WNT9A expression is observed in human OS samples,and c-FOS/LOXL2 co-expression correlates with OS aggressiveness and decreased patient survival.Therefore,therapeutic targeting of Wnt and/or Loxl2 should be considered to potentiate the inadequate current treatments for pediatric,recurrent,and metastatic OS. | Kazuhiko Matsuoka Latifa Bakiri Lena I.Wolff Markus Linder Amanda Mikels-Vigdal Ana Patiño-García Fernando Lecanda Christine Hartmann Maria Sibilia Erwin F.Wagner | 2020 | Cell Research2020，30，10： | 5 |
| 2 | Simplified mammalian DNA isolation procedure显示文摘 | Laird PW Zijderveld A Linders K | 1991 | Nucleic Acids Res1991，19，15： | 2 |
| 3 | Psodisk,a new visual Method for assessing the burden of psoriasis on patients显示文摘 | Linder D Sampogna F Torreggiani A | 2012 | J Eur Acad Dematol Venereol2012，26，9： | 1 |
| 4 | Small acute increases in serum creatinine are associated with decreased long-term survival in the critically ill显示文摘 | Linder A Fjell C Levin A | 2014 | Am J Respir Crit Care Med2014，189，： | 1 |
| 5 | Frey's syndrome after Parotidectomy, a Retrospective and Prospective Analysis 显示文摘 | Linder T E Huber A Schmid S | 1997 | Laymgoscope1997，107，11： | 1 |
| 6 | Evaluation of diagnostic criteria for ankylosing spondylitis: A proposal modification of the New York criteria显示文摘 | van der Linder S ValkenburgHA Cats A | 1984 | Arthritis and Rheumatism1984，27，4： | 1 |
| 7 | Intronic miR-26b controls neuronal differentiation by repressing its host tran-script,etdsp2显示文摘 | Dill H Linder B Fehr A | 2012 | Genes Dev2012，26，1： | 1 |
| 8 | Heparin-binding pro- tein:an early indicator of critical illness and predictor of outcome in cardiac arrest显示文摘 | Dankiewicz J Linder A Annborn M | 2013 | Resuscitation2013，84，7： | 1 |
| 9 | Heparin-binding protein measurement improves the prediction of severe infection with organ dysfunction in the emergency department显示文摘 | Linder A Arnold R Boyd JH | 2015 | Crit Care Med2015，43，11： | 1 |
| 10 | Coordination Chemistry and Catalysis with Hemilabile Oxygen-Phosphorus Ligands显示文摘 | Bader A Linder E | 1991 | Coord Chem Rev1991，108，： | 1 |
| 11 | Concentration of prolaction and proestunplangin during and after cardiopulmonary resncication显示文摘 | Strohmenger Hu linder KH keller A | 1995 | Crit Care Med1995，21，： | 1 |
| 12 | Heparin-binding protein: an early indicator of critical illness and predictor ofoutcome in cardiac arrest 显示文摘 | Dankiewicz J Linder A Annbom M | 2013 | Resuscitation2013，84，7： | 1 |
| 13 | Dirac Fermions and Conductance Oscillations in s-and d-Wave ons显示文摘 | Linder J Sudbo A | 2007 | Phys Rev Lett2007，99，14： | 1 |
| 14 | Early-onset basal cell carcinoma in a case of Ivemark syndrome显示文摘 | Zampetti A Gnarra M Linder D | 2010 | Eur ] Dermatol2010，20，6： | 1 |
| 15 | Rolesofheparin-bindingproteininbacterialinfections显示文摘 | LINDER A SOEHNLEIN O AKESSON P | 2010 | Jour-nalofinnateimmunity2010，2，5： | 1 |
| 16 | Heparin-binding pro- tein:an early marker of circulatory failure in sepsis显示文摘 | Linder A Christensson B Herwald H | 2009 | Clin Infect Dis2009，49，7： | 1 |
| 17 | Tunneling conductance in s-and d-wave superconductor-graphene junctions: Extended Blonder- Tinkham-Klapwijk formalism显示文摘 | Juncti- Linder J Sudbo A | 2008 | Phys Rev B2008，77，06： | 1 |
| 18 | Elevated plasma levels of heparin-binding protein in intensive care unit patients with se vere sepsis and septic shock显示文摘 | Linder A Akesson P Inghammar M | 2012 | Critical Care2012，16，3： | 1 |
| 19 | Influence of hydrolysis degree on the functional properties of salmon byproducts hydrolysates 显示文摘 | GBOGOURI G A LINDER M FANNI J | 2004 | J Food Sci2004，69，： | 1 |
| 20 | Epoxidation of α-olefins by heptane-grown pseudomonas cell显示文摘 | Van der Linder A C | 1963 | Biochem Bioph Acta1963，77，： | 1 |
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