E2F1 impairs all-trans retinoic acid-induced osteogenic differentiation of osteosarcoma via promoting ubiquitination-mediated degradation of RARα

Zhang, Lei; Zhou, Qian; Zhang, Ning; Li, Weixu; Ying, Meidan; Ding, Wanjing; Yang, Bo; He, Qiaojun

doi:10.4161/cc.28190

Cited by 26 publications

(20 citation statements)

References 47 publications

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“…All the cell lines have been tested and authenticated utilizing short tandem repeat (STR) profiling every 6 months. All primary osteosarcoma blasts were from fresh tissue sections from biopsies of osteosarcoma patients as described previously (19). All cells were cultured in DMEM or RPMI-1640 medium supplemented with 10% FBS in a humidified atmosphere of 5% CO 2 at 37 C. The full-length coding sequence for WSB1 and RhoGDI2 was amplified from the U2OS cDNA library and subsequently subcloned into the PCMV6 plasmid (Origene).…”

Section: Cell Lines and Plasmidsmentioning

confidence: 99%

“…1B), suggesting a connection between high WSB1 levels and hypoxic microenvironments. To better understand the effect of hypoxia on WSB1 expression, three osteosarcoma cell lines and two primary osteosarcoma blasts (19) were cultured under hypoxic conditions (1% O 2 ) for 24 hours. The protein expression of WSB1, as well as HIF1a and its downstream target BNIP3, was significantly induced by hypoxia in all five osteosarcoma cells (Fig.…”

Section: Hypoxia-induced Wsb1 Is Highly Associated With Progression Amentioning

confidence: 99%

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Hypoxia-Induced WSB1 Promotes the Metastatic Potential of Osteosarcoma Cells

et al. 2015

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Intratumoral hypoxia occurs in many solid tumors, where it is associated with the development of metastatic character. However, the connections between these phenomena are not fully understood. In this study, we define an integrative role for the E3 ubiquitin ligase subunit WSB1. In primary osteosarcomas, increased levels of WSB1 correlated with pulmonary metastatic potential. RNAi-mediated attenuation of WSB1 or disruption of its E3 ligase activity potently suppressed tumor metastasis. Quantitative proteomic and functional analyses revealed that WSB1 ubiquitylates the Rho-binding protein RhoGDI2 and promotes its proteasomal degradation, thereby activating Rac1 to stimulate tumor cell motility and invasion. Our findings show how WSB1 regulates key steps of the metastatic cascade in hypoxia-driven osteosarcoma, and they highlight a candidate therapeutic target to potentially improve the survival of patients with metastatic disease. Cancer Res; 75(22); 4839-51. Ó2015 AACR.

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Section: Cell Lines and Plasmidsmentioning

confidence: 99%

Section: Hypoxia-induced Wsb1 Is Highly Associated With Progression Amentioning

confidence: 99%

Hypoxia-Induced WSB1 Promotes the Metastatic Potential of Osteosarcoma Cells

et al. 2015

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“…All cells were cultured in DMEM or RPMI1640 medium supplemented with 10% fetal bovine serum (FBS) in a humidified atmosphere of 5% CO 2 at 37°C. All primary osteosarcoma cultures were from fresh tissue sections from biopsies of osteosarcoma patients and maintained in DMEM/F12 medium as previously reported . Written informed consents from patients and approval from the Institutional Research Ethics Committee of the Second Affiliated hospital of Zhejiang University School of Medicine were obtained prior to the use of these clinical materials for research purposes.…”

Section: Methodsmentioning

confidence: 99%

Bortezomib sensitizes human osteosarcoma cells to adriamycin‐induced apoptosis through ROS‐dependent activation of p‐eIF2α/ATF4/CHOP axis

Xian

Cao

et al. 2017

Intl Journal of Cancer

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Osteosarcoma is the most common bone cancer, and chemotherapy is currently indispensable for its treatment. Adriamycin has been claimed to be the most effective agent for osteosarcoma, however, the outcome of adriamycin chemotherapy remains unsatisfactory. Here, we reported a potent combination therapy that bortezomib, a proteasome inhibitor, enhances adriamycin-induced apoptosis to eliminate osteosarcoma cells and we revealed that the activation of p-eIF2α/ATF4/CHOP axis is the underlying associated mechanisms. First, we observed that bortezomib enhances adriamycin-mediated inhibition of cell proliferation and enhances the apoptosis in osteosarcoma cell lines. Moreover, this drug combination produced more potent tumor-growth inhibitory effects in human osteosarcoma cell line KHOS/NP xenografts. Our study showed that reactive oxygen species (ROS) plays an important role in apoptosis induced by adriamycin plus bortezomib, whereas ROS scavenger NAC could almost completely block the apoptosis induced by the combination treatment. Meanwhile, p-eIF2α is remarkably elevated in the combination group. As a result, ATF4 exhibits strong activation which consequently induces the activation of CHOP and leads to the cell death. Finally, 13 primary osteosarcoma cells demonstrated potent response to the combination treatment. In a human osteosarcoma patient-derived xenograft (PDX) model, our finding suggests that when combined with bortezomib, a relatively low dose of adriamycin produced more potent tumor-growth inhibitory effects without increased toxicity. Thus, our findings not only provide a promising combination strategy to overcome osteosarcoma but also shed new light on the strategy of combining increased ROS and inhibited proteasome to open up new opportunities for the clinical development of chemotherapy regimens.

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“…Therefore, the restoration of the osteogenic ability of BMP9 in OS cells may contribute to the treatment of OS. ATRA promotes terminal differentiation of immature cells, including various types of cancer cells (25)(26)(27)(28)(29)(30), and can promote osteogenic differentiation (29)(30)(31)(32)(33)48). Yang et al reported that ATRA could inhibit proliferation, induce apotosis and promote osteogenic differentiation in 143B cells, but the effect of apotosis induced by ATRA is not obvious.…”

Section: Discussionmentioning

confidence: 99%

“…ATRA can induce differentiation in acute promyelocytic leukaemia (APL) and other tumour types, such as neuroblastoma, breast cancer and melanoma (25)(26)(27)(28). Additionally, ATRA can induce osteoblastic differentiation of osteosarcoma cells both in vivo and in vitro (29,30). Luo et al (31) and Ying et al (32) have reported that ATRA-induced osteogenic differentiation is mediated by the retinoid-suppressed phosphorylation of RARα in OS cells.…”

Section: Introductionmentioning

confidence: 99%

All-trans retinoic acid restored the osteogenic ability of BMP9 in osteosarcoma through the p38 MAPK pathway

Meng

et al. 2017

International Journal of Oncology

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Abstract. Osteosarcoma (OS) is the most common malignant bone tumour and is considered to be a disease caused by a dysfunction in differentiation. Bone morphogenetic protein 9 (BMP9) is the most potent osteogenic factor in mesenchymal stem cells, but it cannot induce osteogenic differentiation in OS cells; this might be one of the determinants in the pathogenesis of OS. All-trans retinoic acid (ATRA) can induce osteogenic differentiation of OS cells and potentiate BMP9-induced osteogenesis in preadipocytes. However, the concomitant effect of ATRA and BMP9 in OS cells is unclear; therefore, in the present study, we focused on this topic. The results showed that BMP9 significantly promoted the proliferation of human OS 143B cells and did not induce osteogenic differentiation of cells in vitro (p<0.01). ATRA inhibited proliferation and induced osteogenesis in 143B cells; these effects could be enhanced by BMP9 overexpression (p<0.05). ATRA could significantly increase the level of phosphorylated p38 MAPK (p-p38) in 143B cells, while BMP9 did not have any significant effect. Notably, BMP9 overexpression enhanced the ability of ATRA to increase the levels of p-p38. Both the osteogenic differentiation and the anti-proliferative activity of BMP9 in the presence of ATRA decreased upon treatment with a specific inhibitor of p38 MAPK (SB203580) (p<0.01). This study indicates that the osteogenic differentiation ability of BMP9 in 143B cells can be restored by ATRA, and the combination of BMP9 and ATRA generated a stronger anti-proliferative effect on 143B cells than ATRA alone. This result may be due to the activation of the p38 MAPK pathway.

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E2F1 impairs all-trans retinoic acid-induced osteogenic differentiation of osteosarcoma via promoting ubiquitination-mediated degradation of RARα

Abstract: He (2014) E2F1 impairs all-trans retinoic acid-induced osteogenic differentiation of osteosarcoma via promoting ubiquitination-mediated degradation of RARα, Cell Cycle, 13:8,

Cited by 26 publications

References 47 publications

Hypoxia-Induced WSB1 Promotes the Metastatic Potential of Osteosarcoma Cells

Hypoxia-Induced WSB1 Promotes the Metastatic Potential of Osteosarcoma Cells

Bortezomib sensitizes human osteosarcoma cells to adriamycin‐induced apoptosis through ROS‐dependent activation of p‐eIF2α/ATF4/CHOP axis

All-trans retinoic acid restored the osteogenic ability of BMP9 in osteosarcoma through the p38 MAPK pathway

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