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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 | Mouse models for liver cancer显示文摘 | Latifa Bakiri Erwin F. Wagner | 2013 | Molecular Oncology2013，，： | 2 |
| 3 | Solving multiclass learning problems via error- correcting output codes显示文摘 | Dietterich T G Bakiri G | 1995 | Journal of Artificial Intelligence Research1995，2，： | 1 |
| 4 | Essential role of RSK2 in c-Fos-dependent osteosarcoma development 显示文摘 | David JP Mehic D Bakiri L | 2005 | J Clin Invest2005，115，3： | 1 |
| 5 | Solving multi-class learning problem via error-correcting output codes显示文摘 | DIETTERICH TG BAKIRI G | 1995 | Journal of Artificial Intelligent Research1995，，2： | 1 |
| 6 | Essential role of RSK2 in c - fos dependent osteosarcoma development 显示文摘 | David JP Mehic D Bakiri L | 2005 | J Clin Invest2005，115，： | 1 |
| 7 | Unusual reactions to hymenoptera stings:what should we keep in mind?显示文摘 | Mingomataj E Bakiri AH Ibranji A | 2014 | Clin Rev Allergy Immunol2014，47，1： | 1 |
| 8 | Spiking and nonspik- ing classes of oligodendmcyte precursor glia in CNS white matter显示文摘 | K6rad6ttir R Hamilton NB Bakiri Y | 2008 | Nat Neurosci2008，11，： | 1 |
| 9 | Solving muhiclass learning prob- lems via error-correcting output codes 显示文摘 | On a class of Information and Control Dietterich T G Bakiri G | 1994 | Journal of Arti- ficial Intelligence Research1994，2，1： | 1 |
| 10 | Essential role of RSK2 in c-fos dependent osteosarcoma development显示文摘 | David JP Mehic D Bakiri L | | 0，，： | 1 |
| 11 | p38 alpha: a suppressor of cell proliferation and tumorigenesis显示文摘 | Hui L Bakiri L Stepniak E etal | | Cell Cycle0，6，20： | 1 |
| 12 | Solving multiclass learning problem via error correcting output codes显示文摘 | Ditterich T G Bakiri G | 1995 | Journal of Artificial Intelligence Research1995，11，2： | 1 |
| 13 | Solving multiclass learning problems via error-correcting output codes 显示文摘 | Thomas G D Bakiri G | 1995 | Journal of Artifieal Intelligence Research1995，2，2： | 1 |
| 14 | Cell cycle-dependent variations in C-JLm and JunB phosphorylation: a role in the control of cyclin D1 expression显示文摘 | Bakiri L Lallemand D Bossy-Wetzel E | 2000 | EMBO J2000，19，9： | 1 |
| 15 | Solving multiclass learning problems via error-correcting output codes显示文摘 | Dietterich T G Bakiri G | 1995 | Artificial Intelligence Research1995，2，1： | 1 |
| 16 | Solving multi-class learning problems via error-correcting output Codes显示文摘 | Dietterich T G Bakiri G | 1995 | Journal of Artificial Intelligent Research1995，2，： | 1 |
| 17 | Solving muhiclass learning prob- lems via error-correcting output codes 显示文摘 | Dietterich T G Bakiri G | 1995 | Journal of Arti- ficial Intelligence Research1995，，2： | 1 |
| 18 | Distraction and driving: Results from a case-control responsi- bility study of traffic crash injured drivers inter- viewed at the emergency room显示文摘 | Bakiri S Galara C Lagarde E | 2013 | Accident Anal- ysis & Prevention2013，59，9： | 1 |
| 19 | Effects of arginine and growth hormone on the nitrogen balance of the rat显示文摘 | Elsair J Bakiri F Reggabi M | 1975 | Biomedicine1975，23，6： | 1 |
| 20 | Solving multiclass learning problems via error-correcting output codes显示文摘 | T G Dietterich G Bakiri | 1995 | Journal of Artificial Intelligence Research1995，2，： | 1 |
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