The small heat shock protein B8 (HSPB8) modulates proliferation and migration of breast cancer cells

Margherita Piccolella, Valeria Crippa, Riccardo Cristofani, Paola Rusmini, Mariarita Galbiati, Maria Elena Cicardi, Marco Meroni, Nicola Ferri, Federica F Morelli, Serena Carra, Elio Messi, Angelo Poletti

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Abstract

Breast cancer (BC) is one of the major causes of cancer death in women and is closely related to hormonal dysregulation. Estrogen receptor (ER)-positive BCs are generally treated with anti hormone therapy using antiestrogens or aromatase inhibitors. However, BC cells may become resistant to endocrine therapy, a process facilitated by autophagy, which may either promote or suppress tumor expansion. The autophagy facilitator HSPB8 has been found overexpressed in some BC. Here we found that HSPB8 is highly expressed and differentially modulated by natural or synthetic selective ER modulators (SERMs), in the triple-positive hormone-sensitive BC (MCF-7) cells, but not in triple-negative MDA-MB-231 BC cells. Specific SERMs induced MCF-7 cells proliferation in a HSPB8 dependent manner whereas, did not modify MDA-MB-231 cell growth. ER expression was unaffected in HSPB8-depleted MCF-7 cells. HSPB8 over-expression did not alter the distribution of MCF-7 cells in the various phases of the cell cycle. Conversely and intriguingly, HSPB8 downregulation resulted in an increased number of cells resting in the G0/G1 phase, thus possibly reducing the ability of the cells to pass through the restriction point. In addition, HSPB8 downregulation reduced the migratory ability of MCF-7 cells. None of these modifications were observed, when another small HSP (HSPB1), also expressed in MCF-7 cells, was downregulated. In conclusion, our data suggest that HSPB8 is involved in the mechanisms that regulate cell cycle and cell migration in MCF-7 cells.

Original languageEnglish
Pages (from-to)10400-10415
Number of pages16
JournalOncotarget
Volume8
Issue number6
DOIs
Publication statusPublished - Feb 7 2017

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Keywords

  • Antineoplastic Agents, Hormonal
  • Breast Neoplasms
  • Cell Cycle Checkpoints
  • Cell Movement
  • Cell Proliferation
  • Estrogen Receptor alpha
  • Estrogen Receptor beta
  • Female
  • Gene Expression Regulation, Neoplastic
  • Heat-Shock Proteins
  • Hep G2 Cells
  • Humans
  • MCF-7 Cells
  • Neoplasm Invasiveness
  • Protein-Serine-Threonine Kinases
  • RNA Interference
  • Selective Estrogen Receptor Modulators
  • Signal Transduction
  • Time Factors
  • Transfection
  • Journal Article

Cite this

Piccolella, M., Crippa, V., Cristofani, R., Rusmini, P., Galbiati, M., Cicardi, M. E., Meroni, M., Ferri, N., Morelli, F. F., Carra, S., Messi, E., & Poletti, A. (2017). The small heat shock protein B8 (HSPB8) modulates proliferation and migration of breast cancer cells. Oncotarget, 8(6), 10400-10415. https://doi.org/10.18632/oncotarget.14422