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

  • Authors:
    • Masato Tomonaga
    • Nobuyuki Hashimoto
    • Fuminori Tokunaga
    • Megumi Onishi
    • Akira Myoui
    • Hideki Yoshikawa
    • Kazuhiro Iwai
  • View Affiliations

  • Published online on: September 22, 2011     https://doi.org/10.3892/ijo.2011.1209
  • Pages: 409-417
Metrics: HTML 0 views | PDF 0 views     Cited By (CrossRef): 0 citations

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.

Related Articles

Journal Cover

February 2012
Volume 40 Issue 2

Print ISSN: 1019-6439
Online ISSN:1791-2423

Sign up for eToc alerts

Recommend to Library

Copy and paste a formatted citation
APA
Tomonaga, M., Hashimoto, N., Tokunaga, F., Onishi, M., Myoui, A., Yoshikawa, H., & Iwai, K. (2012). Activation of nuclear factor-kappa B by linear ubiquitin chain assembly complex contributes to lung metastasis of osteosarcoma cells. International Journal of Oncology, 40, 409-417. https://doi.org/10.3892/ijo.2011.1209
MLA
Tomonaga, M., Hashimoto, N., Tokunaga, F., Onishi, M., Myoui, A., Yoshikawa, H., Iwai, K."Activation of nuclear factor-kappa B by linear ubiquitin chain assembly complex contributes to lung metastasis of osteosarcoma cells". International Journal of Oncology 40.2 (2012): 409-417.
Chicago
Tomonaga, M., Hashimoto, N., Tokunaga, F., Onishi, M., Myoui, A., Yoshikawa, H., Iwai, K."Activation of nuclear factor-kappa B by linear ubiquitin chain assembly complex contributes to lung metastasis of osteosarcoma cells". International Journal of Oncology 40, no. 2 (2012): 409-417. https://doi.org/10.3892/ijo.2011.1209