Retinoid-suppressed phosphorylation of RARα mediates the differentiation pathway of osteosarcoma cells

Luo, Peihua; Yang, Xiaochun; Ying, Meidan; Chaudhry, Parvesh; Wang, A; Shimada, Hiroyuki; May, Win; Adams, Gregor B.; Mock, Dennis; Triche, Timothy J.; He, Qiaojun; Wu, Liquan

doi:10.1038/onc.2010.50

Cited by 35 publications

(59 citation statements)

References 55 publications

(81 reference statements)

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“…Since osteoblasts have the properties to synthesize osteopontin (OPN) and stimulate high alkaline phosphatase (ALP) activity, 26,27 western blotting and real-time PCR analysis were performed to evaluate the production of OPN, and BCIP/NBT staining was further applied to detect ALP activity. Our results showed that ATRA induced apparent upregulation of OPN expression and ALP activity in U2OS cells as we previously reported, 14 while there were no active osteoblasts present in E2F1-overexpressed U2OS cells even after ATRA treatment ( Fig. 2A and B).…”

Section: E2f1 Impairs Atra-induced Osteogenic Differentiation In Ostesupporting

confidence: 90%

“…We previously reported that ATRA could effectively induce osteogenic differentiation of U2OS cells; 14 thus, the role of E2F1 was determined by using this established cell model in this study. By overexpressing or silencing E2F1, the differentiation efficiency of ATRA was evaluated.…”

Section: E2f1 Impairs Atra-induced Osteogenic Differentiation In Ostementioning

confidence: 99%

“…Our previous studies reported that retinoic acid receptors play a critical role in ATRA-induced osteogenic differentiation; 14 therefore, we next asked how E2F1 finely regulates ATRAinduced differentiation, and whether RARα is involved. The RARα expression in tissue sections from biopsies of patients was assessed by immunohistochemistry assay first.…”

Section: Rarα Expression Is Inversely Related To the Level Of E2f1 Inmentioning

confidence: 99%

“…[9][10][11][12][13] We, along with others, also have found that ATRA induces osteoblastic differentiation of osteosarcoma cells both in vivo and in vitro. 14,15 Moreover, ATRA has been found to induce osteoblastic differentiation of mouse and rat mesenchymal stem cells and preosteoblasts. 16,17 All these studies suggest that ATRA can restore normal osteogenesis, and ATRA-based differentiation therapeutics might be feasible for osteosarcoma.…”

Section: Introductionmentioning

confidence: 99%

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

et al. 2014

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Section: E2f1 Impairs Atra-induced Osteogenic Differentiation In Ostesupporting

confidence: 90%

Section: E2f1 Impairs Atra-induced Osteogenic Differentiation In Ostementioning

confidence: 99%

Section: Rarα Expression Is Inversely Related To the Level Of E2f1 Inmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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

et al. 2014

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“…It suggests that estrogen receptor and EGFR pathway may be linked together in the regulation of osteogenesis (40). Retinoic acid (RA) suppresses phosphorylation of RA receptor a (RARa) and induces expression of a downstream target, fibroblast growth factor 8f, to mediate the differentiation of osteosarcoma cells (41). Furthermore, activation of PPARg and RAR demonstrates a synergistic effect in inhibiting osteosarcoma cell growth and promoting differentiation of osteosarcoma cells (42).…”

Section: Discussionmentioning

confidence: 99%

Coleusin Factor, a Novel Anticancer Diterpenoid, Inhibits Osteosarcoma Growth by Inducing Bone Morphogenetic Protein-2–Dependent Differentiation

Geng

Sun

et al. 2014

Molecular Cancer Therapeutics

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Coleusin factor is a diterpenoid compound isolated from the root of a tropical plant, Coleus forskohlii. Although Coleusin factor has been reported to suppress proliferation of and induce apoptosis in several types of cancer cells, the effects of Coleusin factor on osteosarcoma and the underlying mechanism are still not fully understood. In this study, we show that Coleusin factor treatment potently inhibits the growth of osteosarcoma cells associated with G 1 cell-cycle arrest. Interestingly, apoptosis and cell death are not induced. Instead, Coleusin factor causes osteosarcoma cells to exhibit typical properties of differentiated osteoblasts, including a morphologic alteration resembling osteoblasts, the expression of osteoblast differentiation markers, elevated alkaline phosphatase activity, and increased cellular mineralization. Coleusin factor treatment significantly increases the expression of bone morphogenetic protein-2 (BMP-2), a crucial osteogenic regulator, and runt-related transcription factor 2 (RUNX2), one of the key transcription factors of the BMP pathway. When BMP-2 signaling is blocked, Coleusin factor fails to inhibit cell proliferation and to induce osteoblast differentiation. Thus, upregulation of BMP-2 autocrine is critical for Coleusin factor to induce osteoblast differentiation and exert its anticancer effects on osteosarcoma. Importantly, administration of Coleusin factor inhibits the growth of osteosarcoma xenografted in nude mice without systemic or immunologic toxicity. Osteosarcoma is a highly aggressive cancer marked by the loss of normal differentiation. Coleusin factor represents a new type of BMP-2 inducer that restores differentiation in osteosarcoma cells. It may provide a promising therapeutic strategy against osteosarcoma with minimal side effects. Mol Cancer Ther; 13(6);

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CD99 Drives Terminal Differentiation of Osteosarcoma Cells by Acting as a Spatial Regulator of ERK 1/2

Sciandra

Marino²,

Manara

et al. 2013

Journal of Bone and Mineral Research

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Differentiation therapy is an attractive treatment for osteosarcoma (OS). CD99 is a cell surface molecule expressed in mesenchymal stem cells and osteoblasts that is maintained during osteoblast differentiation while lost in OS. Herein, we show that whenever OS cells regain CD99, they become prone to reactivate the terminal differentiation program. In differentiating conditions, CD99-transfected OS cells express osteocyte markers, halt proliferation, and largely die by apoptosis, resembling the fate of mature osteoblasts. CD99 induces ERK activation, increasing its membrane-bound/cytoplasmic form rather than affecting its nuclear localization. Through cytoplasmic ERK, CD99 promotes activity of the main osteogenic transcriptional factors AP1 and RUNX2, which in turn enhance osteocalcin and p21WAF1/CIP1, leading to G0/G1 arrest. These data underscore the alternative positions of active ERK into distinct subcellular compartments as key events for determining OS fate. © 2014 The Authors. Journal of Bone and Mineral Research published by Wiley Periodicals, Inc. on behalf of the American Society for Bone and Mineral Research.

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Retinoid-suppressed phosphorylation of RARα mediates the differentiation pathway of osteosarcoma cells

Cited by 35 publications

References 55 publications

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

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

Coleusin Factor, a Novel Anticancer Diterpenoid, Inhibits Osteosarcoma Growth by Inducing Bone Morphogenetic Protein-2–Dependent Differentiation

CD99 Drives Terminal Differentiation of Osteosarcoma Cells by Acting as a Spatial Regulator of ERK 1/2

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