2020
DOI: 10.1038/s41422-020-0370-1
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Wnt signaling and Loxl2 promote aggressive osteosarcoma

Abstract: 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 Ze… Show more

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Cited by 85 publications
(65 citation statements)
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References 78 publications
(84 reference statements)
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“…Osteosarcoma (OS) is a primary malignant bone tumour that commonly affects children and adolescents 1,2 . Despite progress in chemotherapy and surgical approaches, the survival rate of OS is still unsatisfactory because of frequent lung metastasis 3 .…”
Section: Introductionmentioning
confidence: 99%
See 1 more Smart Citation
“…Osteosarcoma (OS) is a primary malignant bone tumour that commonly affects children and adolescents 1,2 . Despite progress in chemotherapy and surgical approaches, the survival rate of OS is still unsatisfactory because of frequent lung metastasis 3 .…”
Section: Introductionmentioning
confidence: 99%
“…Osteosarcoma (OS) is a primary malignant bone tumour that commonly affects children and adolescents. 1 , 2 Despite progress in chemotherapy and surgical approaches, the survival rate of OS is still unsatisfactory because of frequent lung metastasis. 3 Hence, a deeper understanding of the underlying molecular mechanisms of OS progression and the identification of molecular targets that are dependent on complex gene regulation networks are urgently needed.…”
Section: Introductionmentioning
confidence: 99%
“…cAMP-regulating cascades activate Wnt signaling through GSK3β phosphorylation and β-catenin nuclear translocation. Wnt signaling plays significant roles in the progression of multiple tumors [26,[44][45][46][47], and was required for GSC development and self-renewal [26]. The deficiency of Wnt/ β-catenin signaling repressed glioma progression [48][49][50].…”
Section: Discussionmentioning
confidence: 99%
“…The canonical Wnt pathway is highly evolutionary conserved and affects β-catenin. Previous studies evidence that WNT7B initiates βcatenin to regulate the occurence and development of bone disorders, including (16,17). For instance, Chen et al (18) reveal that WNT7B WNT7B rescues glucocorticoid-induced bone loss and suppresses secondary cause for osteoporosis.…”
Section: Introductionmentioning
confidence: 99%