Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2012 Feb;40(2):409-17.
doi: 10.3892/ijo.2011.1209. Epub 2011 Sep 22.

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

Masato Tomonaga  1 , Nobuyuki Hashimoto, Fuminori Tokunaga, Megumi Onishi, Akira Myoui, Hideki Yoshikawa, Kazuhiro Iwai
Affiliations

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

Masato Tomonaga et al. Int J Oncol. 2012 Feb.

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.

PubMed Disclaimer

Similar articles

See all similar articles

Cited by

See all "Cited by" articles

Publication types

MeSH terms

LinkOut - more resources