Transfection of NF-κB decoy oligodeoxynucleotide suppresses pulmonary metastasis by murine osteosarcoma

Nishimura, Akinobu; Akeda, Koji; Matsubara, Takehiro; Kusuzaki, Katsuyuki; Matsumine, Akihiko; Masuda, Koichi; Gemba, Takefumi; Uchida, Atsushi; Sudo, Akihiro

doi:10.1038/cgt.2010.75

Cited by 32 publications

(29 citation statements)

References 42 publications

(51 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…NF-κB has also been reported to have a central and specific role in the regulation of metastasis in LM8 cells, because NF-κB decoy transfection inhibited pulmonary metastasis of these cells. 27 In the present study, phosphorylation levels of FAK at the cell protrusion region and NF-κB activity were suppressed in shPP2A cells, suggesting that PP2A Cα regulates cell migration and metastasis by controlling FAK and NF-κB activity.…”

Section: Discussionsupporting

confidence: 55%

Protein phosphatase 2A Cα regulates proliferation, migration, and metastasis of osteosarcoma cells

Yang

Okamura

Morimoto

et al. 2016

Laboratory Investigation

View full text Add to dashboard Cite

Osteosarcoma is the most frequent primary bone tumor. Serine/threonine protein phosphatase 2A (PP2A) participates in regulating many important physiological processes, such as cell cycle, growth, apoptosis, and signal transduction. In this study, we examined the expression and function of PP2A Cα in osteosarcoma cells. PP2A Cα expression was expected to be higher in malignant osteosarcoma tissues. PP2A Cα expression level and PP2A activity was higher in malignant osteosarcoma LM8 cells compared with that in primary osteoblasts and in the osteoblast-like cell line MC3T3-E1. Okadaic acid, an inhibitor of PP2A, reduced cell viability and induced apoptosis in LM8 cells. PP2A Cα-knockdown LM8 cells (shPP2A) exhibited less striking filopodial and lamellipodial structures than that in original LM8 cells. Focal adhesion kinase phosphorylation and NF-κB activity decreased in shPP2A-treated cells. Sensitivity to serum deprivation-induced apoptosis increased in shPP2A-treated cells, accompanied by a lower expression level of anti-apoptotic BCL-2 in these cells. Reduction of PP2A Cα resulted in a decrease in the migration ability of LM8 cells in vitro. Reduction in PP2A Cα levels in vivo suppressed proliferation and metastasis in LM8 cells. PP2A Cα expression was also higher in human osteosarcoma MG63 and SaOS-2 cells than that in primary osteoblasts and MC3T3-E1 cells, and reduction in PP2A Cα levels suppressed the cell proliferation rate and migration ability of MG63 cells. These results indicate that PP2A Cα has a critical role in the proliferation and metastasis of osteosarcoma cells; therefore, its inhibition could potentially suppress the malignancy of osteosarcoma cells.

show abstract

Section: Discussionsupporting

confidence: 55%

Protein phosphatase 2A Cα regulates proliferation, migration, and metastasis of osteosarcoma cells

Yang

Okamura

Morimoto

et al. 2016

Laboratory Investigation

View full text Add to dashboard Cite

show abstract

“…We have also shown that continu- ously activated NF-κB is related to the high incidence of lung metastasis of LM8 cells (6)(7)(8). LUBAC-induced linear polyubiquitination plays crucial roles in NF-κB activation, and induced expression of LUBAC augments NF-κB activation (19)(20)(21).…”

Section: Discussionmentioning

confidence: 75%

“…We have previously observed that NF-κB is involved in the initial stage of lung metastasis of LM8 osteosarcoma cells (7) and that the induction of LUBAC components enhances NF-κB activation (20). Therefore, we evaluated the expression levels of the LUBAC subunits (HOIP, HOIL-1L, and SHARPIN) in Dunn and LM8 cells to investigate the potential involvement of LUBAC-mediated NF-κB activation in the lung metastasis of osteosarcoma cells.…”

Section: Resultsmentioning

confidence: 99%

“…Nuclear factor-kappa B (NF-κB) was constitutively activated in LM8 cells, and NF-κB-related genes such as matrix metalloproteinase (MMP), vascular endothelial growth factor (VEGF) and intracellular adhesion molecule-1 (ICAM-1) were up-regulated in LM8 cells as compared to the parental Dunn cells (5)(6)(7). Since the constitutive activation of NF-κB is related to the highly metastatic potential of LM8 cells, we performed a therapeutic experiment using parthenolide (PAL), a natural NF-κB inhibitor obtained from an herbal extract (8).…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Activation of nuclear factor-kappa B by linear ubiquitin chain assembly complex contributes to lung metastasis of osteosarcoma cells

Tomonaga

Hashimoto²,

Tokunaga³

et al. 2011

Int J Oncol

View full text Add to dashboard Cite

Abstract. NF-κB is involved in the metastasis of malignant cells. We have shown that NF-κB activation is involved in the pulmonary metastasis of LM8 cells, a highly metastatic subclone of Dunn murine osteosarcoma cells. Recently, it was determined that a newly identified type of polyubiquitin chain, a linear polyubiquitin chain, which is specifically generated by the linear ubiquitin chain assembly complex (LUBAC), plays a critical role in NF-κB activation. Here, we have evaluated the roles of LUBAC-mediated NF-κB activation in the development of lung metastasis of osteosarcoma cells. All three components of LUBAC (HOIL-1L, HOIP and SHARPIN) were highly expressed in LM8 cells compared to Dunn cells. Attenuation of LUBAC expression by stable knockdown of HOIL-1L in LM8 cells significantly suppressed NF-κB activity, invasiveness in vitro and lung metastasis. Induction of intracellular adhesion molecule-1 (ICAM-1) expression by LUBAC is involved in cell retention in the lungs after an intravenous inoculation of tumor cells. Moreover, we found that knockdown of LUBAC decreased not only the number but also the size of the metastatic nodules of LM8 cells in the lungs. These results indicate that LUBAC-mediated NF-κB activation plays crucial roles in several steps involved in metastasis, including extravasation and growth of osteosarcoma cells in the lung, and that suppression of LUBAC-mediated linear polyubiquitination activity may be a new approach to treat this life-threatening disease of young adolescents.

show abstract

“…Han [157]. DNA decoys are double stranded oligonucleotides recognized by DNA-binding proteins, hence trapping them and depleting their function [158][159][160]. Transfection of SATB1 decoy DNAs significantly reduced proliferative capacity of MDA-MB231 cells and drastically abolished their invasive and metastatic potential.…”

Section: Therapeutic Approach-satb1 As Molecu-lar Targetmentioning

confidence: 99%

Chromatin Organizer SATB1 As a Novel Molecular Target for Cancer Therapy

Mir¹,

Pradhan²,

Galande

2012

CDT

View full text Add to dashboard Cite

Cancer progression and metastasis involve series of alterations in the expression of multitude of genes. The structure and organization of chromatin play an important role in spatial arrangement of genes inside the nucleus thereby allowing different machineries to activate or silence the transcription of genes governed by various epigenetic events. Epigenetic modifications and dynamic changes in chromatin organization by organizer proteins have recently been shown to play an instrumental role in regulating cancer-promoting genes. Special AT-rich binding protein (SATB1) is a unique type of global regulator that integrates higher-order chromatin organization with regulation of gene expression. Aberrant expression of SATB1 has been shown to promote breast, hepatocellular, prostate and various other cancers. In this review we highlight upon the role of SATB1in chromatin organization and as global regulator of gene expression during cancer development. The expression of SATB1 progressively increases with the progression of cancers and it dynamically reprograms the expression of genes that are involved in epithelial-mesenchymal transition. SATB1 directly regulates the expression of ERRB2, MMP2, ABL1, E-cadherin and hence acts as key regulator in cancer development. Understanding the molecular mechanisms of regulation of SATB1 expression would therefore be extremely essential towards designing strategies to control it. Recent studies have provided important insights into regulation of SATB1 by FOXP3 and microRNAs. In this review we evaluate the potential of SATB1 as molecular target for cancer therapy.

show abstract

Transfection of NF-κB decoy oligodeoxynucleotide suppresses pulmonary metastasis by murine osteosarcoma

Cited by 32 publications

References 42 publications

Protein phosphatase 2A Cα regulates proliferation, migration, and metastasis of osteosarcoma cells

Protein phosphatase 2A Cα regulates proliferation, migration, and metastasis of osteosarcoma cells

Activation of nuclear factor-kappa B by linear ubiquitin chain assembly complex contributes to lung metastasis of osteosarcoma cells

Chromatin Organizer SATB1 As a Novel Molecular Target for Cancer Therapy

Contact Info

Product

Resources

About