Cell adhesion induces overexpression of chromodomain helicase/ATPase DNA binding protein 1-like gene (CHD1L) and contributes to cell adhesion-mediated drug resistance (CAM-DR) in multiple myeloma cells

Leuk Res. 2016 Aug:47:54-62. doi: 10.1016/j.leukres.2016.05.007. Epub 2016 May 12.

Abstract

Previous studies have shown that chromodomain helicase/ATPase DNA binding protein 1-like gene (CHD1L) exerts its anti-apoptotic function in many solid cancers. However, its role in human multiple myeloma (MM) has not been thoroughly elucidated. In this study, we investigate the role of CHD1L in MM. Preliminarily, up-regulation and down-regulation assay verified that CHD1L exerts its anti-apoptotic role through the apoptotic pathway involving caspase-9-caspase-3 apoptotic pathway in MM cells. In addition, we determined that CHD1L expression is increased when MM cells were adhered to fibronectin (FN) or bone marrow stromal cell line HS-5 cells and cell adhesion assay indicated that CHD1L siRNA reversed the high cell adhesion rate. Consistent with the reduced adhesion rate, the cells translated to a compromised cell adhesion-mediated drug resistance (CAM-DR) phenotype in MM. In summary, we will propose strategies for developing a CHD1L inhibitor for potential treatment of MM.

Keywords: Apoptosis; CAM-DR; CHD1L; Multiple myeloma.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Apoptosis Regulatory Proteins / metabolism
  • Bone Marrow Cells
  • Cell Adhesion / drug effects
  • Cell Adhesion / physiology*
  • Cell Line, Tumor
  • DNA Helicases / genetics*
  • DNA-Binding Proteins / genetics*
  • Drug Resistance, Neoplasm / genetics*
  • Humans
  • Multiple Myeloma / pathology*
  • RNA, Small Interfering / pharmacology
  • Stromal Cells
  • Up-Regulation

Substances

  • Apoptosis Regulatory Proteins
  • DNA-Binding Proteins
  • RNA, Small Interfering
  • DNA Helicases
  • CHD1 protein, human