Translocation of heparanase into nucleus results in cell differentiation

Tetsuji Nobuhisa, Yoshio Naomoto, Takaomi Okawa, Munenori Takaoka, Mehmet Gunduz, Takayuki Motoki, Hitoshi Nagatsuka, Hidetsugu Tsujigiwa, Yasuhiro Shirakawa, Tomoki Yamatsuji, Minoru Haisa, Junji Matsuoka, Junichi Kurebayashi, Motowo Nakajima, Shun'ichiro Taniguchi, Junji Sagara, Jian Dong, Noriaki Tanaka

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34 Citations (Scopus)

Abstract

We recently reported that heparanase, one of the extracellular matrix-degrading enzymes, which plays a critical role in cancer progression, is located not only in the cytoplasm but also in the nucleus. Here we identified nuclear translocation of heparanase as a key step in cell differentiation. We applied an in vitro differentiation model of HL-60 cells with 12-0-tetradecanoylphorbol-13-acetate (TPA), in which nuclear translocation of heparanase was observed using immunohistochemical analysis. In this system, nuclear translocation of heparanase was abolished by inhibitors of heat shock protein 90 (HSP90), suggesting the involvement of HSP90 in translocation of heparanase. We further confirmed that overexpression of active form of heparanase induced differentiation of HL-60 cells, although the catalytic negative form of heparanase did not. Therefore we speculate that nuclear translocation of enzymatically active heparanase may be involved in cellular differentiation. Our results suggest that a novel function of heparanase upon cell differentiation would raise a potential new strategy for cancer therapy of promyeloid leukemia and other types of cancer.

Original languageEnglish
Pages (from-to)535-540
Number of pages6
JournalCancer Science
Volume98
Issue number4
DOIs
Publication statusPublished - Apr 1 2007

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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  • Cite this

    Nobuhisa, T., Naomoto, Y., Okawa, T., Takaoka, M., Gunduz, M., Motoki, T., Nagatsuka, H., Tsujigiwa, H., Shirakawa, Y., Yamatsuji, T., Haisa, M., Matsuoka, J., Kurebayashi, J., Nakajima, M., Taniguchi, S., Sagara, J., Dong, J., & Tanaka, N. (2007). Translocation of heparanase into nucleus results in cell differentiation. Cancer Science, 98(4), 535-540. https://doi.org/10.1111/j.1349-7006.2007.00420.x