The Wnt signaling pathway: implications for therapy in osteosarcoma

McQueen, Peter; Ghaffar, Samia; Guo, Yi; Rubin, Elyssa; Zi, Xiaolin; Hoang, Bang H.

doi:10.1586/era.11.94

Cited by 73 publications

(61 citation statements)

References 76 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Several Wnt ligands, receptors, and coreceptors are highly expressed in osteosarcoma cell lines, while Wnt inhibitors are downregulated (McQueen et al, 2011). In fact, the role of Wnt in the development of osteosarcoma has been widely reported (Brun et al, 2013;Yang and Zhang, 2013), and has aroused scientific interests worldwide.…”

Section: Discussionmentioning

confidence: 99%

Wnt1-induced MAFK expression promotes osteosarcoma cell proliferation

Wang

Zheng

et al. 2015

Genet. Mol. Res.

View full text Add to dashboard Cite

ABSTRACT. Osteosarcoma is one of the most common primary bone tumors in children and young adults. In this study, we investigated the role of musculoaponeurotic fibrosarcoma oncogene homolog K (MAFK) in osteosarcoma cell proliferation in vitro and the possible pathways that contributed to MAFK-related osteosarcoma development. We first reported that MAFK was expressed at low levels in an osteosarcoma cell line. Furthermore, a significant correlation between MAFK and the Wnt signaling pathway was observed in osteosarcoma by using a gene microarray assay. We found that expression of MAFK could be induced by Wnt1 in a dose-dependent manner. Furthermore, Wnt1-induced MAFK expression caused a significant increase of cell viability, whereas a Wnt pathway inhibitor, IWR-1-endo, abolished Wnt1-induced effects on MAFK. Finally, cell cycle analysis showed that enhanced cell proliferation might be attributed to re-distribution of the cell cycle. Together, our results suggested that Wnt1-induced MAFK expression promoted cell proliferation in MG63 cells, and that the role of MAFK in osteosarcoma might be closely linked to the Wnt signaling pathway.

show abstract

Section: Discussionmentioning

confidence: 99%

Wnt1-induced MAFK expression promotes osteosarcoma cell proliferation

Wang

Zheng

et al. 2015

Genet. Mol. Res.

View full text Add to dashboard Cite

show abstract

“…A better understanding of the underlying mechanism of the carcinogenesis of osteosarcoma is crucial for the diagnosis of and the treatment for osteosarcoma. A variety of signaling pathways, such as hedgehog [3], vascular endothelial growth factor (VEGF) [4, 5], platelet-derived growth factor (PDGF) [6], Wnt [7] and signal transducer and activator of transcription (STAT) pathways [8], have been demonstrated to mediate cell proliferation, apoptosis or invasion of osteosarcoma cells.…”

Section: Introductionmentioning

confidence: 99%

Serine/Threonine Kinase 35, a Target Gene of STAT3, Regulates the Proliferation and Apoptosis of Osteosarcoma Cells

Liu

et al. 2018

Cell Physiol Biochem

View full text Add to dashboard Cite

Background/Aims: Serine/threonine kinase 35 (STK35) may be associated with Parkinson disease and human colorectal cancer, but there have been no reports on the expression levels or roles of STK35 in osteosarcoma. Methods: STK35 mRNA expression was determined in osteosarcoma and bone cyst tissues by real-time PCR. Cell proliferation and apoptosis were assessed by Cell Counting Kit-8 (CCK-8) assay and flow cytometry analysis, respectively. Results: STK35 was up-regulated in osteosarcoma tissues as indicated by analyzing publicly available expression data (GEO dataset E-MEXP-3628) and real-time PCR analysis on our own cohort. We subsequently investigated the effects of STK35 knockdown on two osteosarcoma cell lines, MG63 and U2OS. STK35 knockdown inhibited the growth of osteosarcoma cells in vitro and in xenograft tumors. Meanwhile, STK35 knockdown enhanced apoptosis. Expression of the active forms and the activity of two major executioner caspases, caspase 3 and caspase 7, were also increased in osteosarcoma cells with STK35 silenced. Additionally, Gene Set Enrichment Analysis (GSEA) identified that the JAK/STAT signaling pathway was positively correlated with STK35 expression. The mRNA expression of STK35 was repressed by STAT3 small interfering RNA (siRNA), but not by siRNA of STAT4, STAT5A or STAT6. A luciferase reporter assay further demonstrated that STAT3 transcriptionally regulated STK35 expression. A chromatin immunoprecipitation (ChIP) assay confirmed the direct recruitment of STAT3 to the STK35 promoter. The promotion effects of STAT3 knockdown on cell apoptosis were partially abolished by STK35 overexpression. Furthermore, STK35 mRNA expression was positively correlated with STAT3 mRNA expression in osteosarcoma tissues by Pearson correlation analysis. Conclusions: These results collectively reveal that STAT3 regulates the transcription of STK35 in osteosarcoma. STK35 may exert an oncogenic role in osteosarcoma.

show abstract

“…Even with early diagnosis and aggressive treatment, the prognosis for OS remains poor. Molecular mechanisms underlying disease progression remain poorly understood [2,3]. Therefore, a better understanding of the underlying mechanisms of human osteosarcoma development and progression, as well as identifying molecular targets, is necessary to find effective therapeutic interventions.…”

Section: Introductionmentioning

confidence: 99%

MicroRNA-375 functions as a tumor suppressor in osteosarcoma by targeting PIK3CA

Shi

Chu

et al. 2015

Tumor Biol.

View full text Add to dashboard Cite

Osteosarcoma has become one of the most common primary malignant bone tumors in childhood and adult. Numerous studies have demonstrated that aberrant microRNA (miRNA) expression is involved in human disease including cancer. To date, the potential miRNAs regulating osteosarcoma growth and progression are not fully identified yet. Herein, we showed that miR-375 was frequently downregulated in osteosarcoma tissue and cell lines compared to normal human colon tissues. Overexpression of miR-375 resulted in decreased expression of PIK3CA (phosphatidylinositol-4,5-bisphosphate 3-kinase, catalytic subunit alpha) at both mRNA and protein levels. We found that miR-375 overexpression markedly suppressed cell proliferation in vitro. And inhibition of miR-375 promotes osteosarcoma growth. Mechanistic studies showed that PIK3CA was a potential target of miR-375 and it mediated reduction of PIK3CA resulted in suppression of PI3K/Akt pathway. Taken together, our results demonstrate that miR-375 functions as a growth-suppressive miRNA and plays an important role in inhibiting the tumorigenesis through targeting PIK3CA in osteosarcoma.

show abstract

The Wnt signaling pathway: implications for therapy in osteosarcoma

Cited by 73 publications

References 76 publications

Wnt1-induced MAFK expression promotes osteosarcoma cell proliferation

Wnt1-induced MAFK expression promotes osteosarcoma cell proliferation

Serine/Threonine Kinase 35, a Target Gene of STAT3, Regulates the Proliferation and Apoptosis of Osteosarcoma Cells

MicroRNA-375 functions as a tumor suppressor in osteosarcoma by targeting PIK3CA

Contact Info

Product

Resources

About