Targeting of cancer stem cells by differentiation therapy

Yoshimi Arima, Hiroyuki Nobusue, Hideyuki Saya

Research output: Contribution to journalArticlepeer-review

31 Citations (Scopus)


Chemoresistance is a hallmark of cancer stem cells (CSCs). To develop novel therapeutic strategies that target CSCs, we established osteosarcoma-initiating (OSi) cells by introducing the c-Myc gene into bone marrow stromal cells derived from Ink4a/Arf KO mice. These OSi cells include bipotent committed cells (similar to osteochondral progenitor cells) with a high tumorigenic activity as well as tripotent cells (similar to mesenchymal stem cells) of low tumorigenicity. We recently showed that the tripotent OSi cells are highly resistant to chemotherapeutic agents, and that depolymerization of the actin cytoskeleton in these cells induces their terminal adipocyte differentiation and suppresses their tumorigenicity. We here provide an overview of modulation of actin cytoskeleton dynamics associated with terminal adipocyte differentiation in osteosarcoma as well as discuss the prospects for new therapeutic strategies that target chemoresistant CSCs by inducing their differentiation.

Original languageEnglish
Pages (from-to)2689-2695
Number of pages7
JournalCancer science
Issue number8
Publication statusPublished - 2020 Aug 1


  • actin
  • adipocyte
  • cancer stem cell
  • differentiation
  • osteosarcoma

ASJC Scopus subject areas

  • Oncology
  • Cancer Research


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