Role of GLI2 in the growth of human osteosarcoma

Nagao, Hiroshi; Ijiri, Kosei; Hirotsu, Masataka; Ishidou, Yasuhiro; Yamamoto, Takuya; Nagano, Satoshi; Takizawa, Takumi; Nakashima, Kinichi; Komiya, Setsuro; Setoguchi, Takao

doi:10.1002/path.2880

Cited by 64 publications

(85 citation statements)

References 51 publications

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“…Similarly, inhibition of smoothened, a key molecule in the Hedgehog pathway, slowed the growth of OS cells via the suppression of Skp2 and cyclin D1 and E1, but upregulation of p21 (44). In line with this, knockdown of Gli2, a key mediator of the Hedgehog pathway, prevented OS growth and anchorage-independent growth, and promoted G1 phase arrest through inhibition of Skp2 and cyclin D1 (45). In the present study, depletion of Skp2 in OS cells inhibited cell growth, arrested the G1 cell cycle, triggered cell apoptosis, and suppressed cell migration.…”

Section: Discussionmentioning

confidence: 67%

Inhibition of Skp2 suppresses the proliferation and invasion of osteosarcoma cells

Ding

Han

et al. 2017

Oncology Reports

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Abstract. Osteosarcoma (OS) is a common bone tumor that mainly affects children and young adults. S-phase kinase-associated protein 2 (Skp2) has been characterized to play a critical oncogenic role in a variety of human malignancies. However, the biological function of Skp2 in OS remains largely obscure. In the present study, we elucidated the role of Skp2 in cell growth, cell cycle, apoptosis and migration in OS cells. We found that depletion of Skp2 inhibited cell growth in both MG-63 and SW 1353 cells. Moreover, we observed that depletion of Skp2 triggered cell apoptosis in two OS cell lines. Furthermore, downregulation of Skp2 induced cell cycle arrest in the G0/G1 phase in OS cells. Notably, our wound healing assay results revealed that inhibition of Skp2 suppressed cell migration in OS cells. Invariably, our western blot results demonstrated that depletion of Skp2 in OS cells inhibited activation of pAkt and increased p27 expression in OS cells, suggesting that Skp2 exerted its oncogenic function partly through the regulation of Akt and p27. Our findings revealed that targeting Skp2 could be a promising therapeutic strategy for the treatment of OS.

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Section: Discussionmentioning

confidence: 67%

Inhibition of Skp2 suppresses the proliferation and invasion of osteosarcoma cells

Ding

Han

et al. 2017

Oncology Reports

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“…In addition, over-expression of GLI2 promoted mesenchymal stem cell proliferation and accelerated their cell cycle progression. GLI2 knockdown inhibited the growth of OSA in nude mice (Nagao et al, 2011). Suggesting that inhibition of GLI2 represent an effective therapeutic approach for patients with OSA.…”

Section: Gli2 Transcription Factor Accelerated the Progression Of Osamentioning

confidence: 93%

“…The GLI transcription factors exist as three separate zinc-finger proteins, GLI 1 and GLI 2 functioning as transcriptional activators and GLI 3 as a transcriptional repressor (Ruiz, 1997). GLI2 was aberrantly over-expressed in human OSA biopsy specimens (Hirotsu et al, 2010;Nagao et al, 2011). GLI2 knockdown by RNA interferences prevented OSA growth and anchorage-independent growth (Hirotsu et al, 2010;Nagao et al, 2011).…”

Section: Gli2 Transcription Factor Accelerated the Progression Of Osamentioning

confidence: 99%

“…GLI2 was aberrantly over-expressed in human OSA biopsy specimens (Hirotsu et al, 2010;Nagao et al, 2011). GLI2 knockdown by RNA interferences prevented OSA growth and anchorage-independent growth (Hirotsu et al, 2010;Nagao et al, 2011). Knockdown of GLI2 promoted the arrest of OSA cells in G (1) phase and was accompanied by reduced protein expression of the cell cycle accelerators cyclin D1, SKP2 and phosphorylated Rb (Nagao et al, 2011).…”

Section: Gli2 Transcription Factor Accelerated the Progression Of Osamentioning

confidence: 99%

“…GLI2 knockdown by RNA interferences prevented OSA growth and anchorage-independent growth (Hirotsu et al, 2010;Nagao et al, 2011). Knockdown of GLI2 promoted the arrest of OSA cells in G (1) phase and was accompanied by reduced protein expression of the cell cycle accelerators cyclin D1, SKP2 and phosphorylated Rb (Nagao et al, 2011). On the other hand, knockdown of GLI2 increased the expression of p21 (cip1) ( Hirotsu et al, 2010).…”

Section: Gli2 Transcription Factor Accelerated the Progression Of Osamentioning

confidence: 99%

See 2 more Smart Citations

Review of the Molecular Pathogenesis of Osteosarcoma

Hao²,

Wang³

et al. 2014

Asian Pacific Journal of Cancer Prevention

123

109

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Treating the osteosarcoma (OSA) remains a challenge. Current strategies focus on the primary tumor and have limited efficacy for metastatic OSA. A better understanding of the OSA pathogenesis may provide a rational basis for innovative treatment strategies especially for metastases. The aim of this review is to give an overview of the molecular mechanisms of OSA tumorigenesis, OSA cell proliferation, apoptosis, migration, and chemotherapy resistance, and how improved understanding might contribute to designing a better treatment target for OSA.

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GANT61 plays antitumor effects by inducing oxidative stress through the miRNA‐1286/RAB31 axis in osteosarcoma

Zhang

Chu

2020

Cell Biology International

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Osteosarcoma (OS) is a rare malignancy of bone associated with poor clinical outcomes. The antitumor effects of GANT61 on OS is unclear. To investigate antitumor effects and mechanism of GANT61 in OS cells and xenograft model. Effects of GANT61 on cell viability, clone formation, cell cycle, apoptosis, migration, and invasion ability of OS cells were assessed. Reactive oxygen species (ROS) levels measured by dichlorofluorescein fluorescence were used to evaluate oxidative stress. The Xenograft model was constructed to investigate the antitumor effects of GANT61 in vivo. The microRNA (miRNA)‐1286 was downregulated, while RAB31 upregulated in OS tissues and cells. GANT61 inhibited viability, migration, and invasion ability of OS cells (SaOS‐2 and U2OS), and induced apoptosis and the ROS production, along with miRNA‐1286 upregulation and RAB13 downregulation. After knockdown of miRNA‐1286, GANT6‐induced cell inhibition was attenuated, along with RAB31 upregulation. Inversely, miRNA‐1286 overexpression downregulated RAB31. Dual‐luciferase reporter assay verified that miR‐1286 negatively targeted RAB13. Moreover, the knockdown of RAB31 stimulated apoptosis and ROS production while inhibited viability, migration, and invasion of GANT61‐treated cells. In vivo experiments further confirmed that GANT61 inhibited tumor growth and RAB13 expression, but enhanced miRNA‐1286. The study demonstrated that GANT61 inhibited cell aggressive phenotype and tumor growth by inducing oxidative stress through the miRNA‐1286/RAB31 axis. Our findings provided a potential antitumor agent for the OS clinical treatment.

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Role of GLI2 in the growth of human osteosarcoma

Cited by 64 publications

References 51 publications

Inhibition of Skp2 suppresses the proliferation and invasion of osteosarcoma cells

Inhibition of Skp2 suppresses the proliferation and invasion of osteosarcoma cells

Review of the Molecular Pathogenesis of Osteosarcoma

GANT61 plays antitumor effects by inducing oxidative stress through the miRNA‐1286/RAB31 axis in osteosarcoma

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