Histone deacetylase inhibitors induce CXCR4 mRNA but antagonize CXCR4 migration

Caterina Ierano, Agnes Basseville, Kenneth K W To, Zhirong Zhan, Robert W. Robey, Julia Wilkerson, Susan E. Bates, Stefania Scala

Research output: Contribution to journalArticle

Abstract

The stromal cell-derived factor-1a SDF-1a (CXCL12)/CXCR4 axis has been linked to poor prognosis in some cancers. As histone deacetylase inhibitors (HDIs) exert antitumor effects by targeting proteins affecting cell migration, we sought to evaluate the effects of the HDIs apicidin, vorinostat, entinostat (MS-275) and romidepsin on the expression and function of CXCR4 in human cancer cell lines. After treatment with romidepsin, CXCR4 mRNA expression increased 12-fold in UOK121 renal cancer cells, 16-fold in H460 non-small cell cancer cells and 4-fold in SF295 glioma cells; treatment with other HDIs yielded similar effects. CXCR4 induction was not observed in MCF7 breast cancer cells or SW620 colon cancer cells. To evaluate the corresponding functional increase, the effect of CXCR4 ligand, CXCL12, on ERK1/2, STAT3 and c-SRC activation and cell migration was examined in UOK121, SF295 and H460 cells. Alone, the HDIs increased pERK1/2, while reducing pSTAT-3 and pSRC. Following CXCL12 exposure, pERK1/2 induction was maintained, but STAT3 and SRC phosphorylation was impaired. These findings resulted in reduced basal and CXCL12-mediated cell migration. In conclusion, HDIs upregulated CXCR4 mRNA expression but impaired CXCL12-dependent signaling cascades through STAT3 and c-SRC, suggesting a potential role for HDIs in delaying or preventing metastatic processes in solid tumors.

Original languageEnglish
Pages (from-to)175-183
Number of pages9
JournalCancer Biology and Therapy
Volume14
Issue number2
DOIs
Publication statusPublished - Feb 2013

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Histone Deacetylase Inhibitors
Messenger RNA
Cell Movement
Neoplasms
Protein Transport
Stromal Cells
Renal Cell Carcinoma
Glioma
Colonic Neoplasms
Phosphorylation
Breast Neoplasms
Ligands
Cell Line

Keywords

  • CXCL12
  • CXCR4
  • Histone deacetylase inhibitor
  • Migration
  • Romidepsin

ASJC Scopus subject areas

  • Cancer Research
  • Oncology
  • Molecular Medicine
  • Pharmacology

Cite this

Ierano, C., Basseville, A., To, K. K. W., Zhan, Z., Robey, R. W., Wilkerson, J., ... Scala, S. (2013). Histone deacetylase inhibitors induce CXCR4 mRNA but antagonize CXCR4 migration. Cancer Biology and Therapy, 14(2), 175-183. https://doi.org/10.4161/cbt.22957

Histone deacetylase inhibitors induce CXCR4 mRNA but antagonize CXCR4 migration. / Ierano, Caterina; Basseville, Agnes; To, Kenneth K W; Zhan, Zhirong; Robey, Robert W.; Wilkerson, Julia; Bates, Susan E.; Scala, Stefania.

In: Cancer Biology and Therapy, Vol. 14, No. 2, 02.2013, p. 175-183.

Research output: Contribution to journalArticle

Ierano, C, Basseville, A, To, KKW, Zhan, Z, Robey, RW, Wilkerson, J, Bates, SE & Scala, S 2013, 'Histone deacetylase inhibitors induce CXCR4 mRNA but antagonize CXCR4 migration', Cancer Biology and Therapy, vol. 14, no. 2, pp. 175-183. https://doi.org/10.4161/cbt.22957
Ierano C, Basseville A, To KKW, Zhan Z, Robey RW, Wilkerson J et al. Histone deacetylase inhibitors induce CXCR4 mRNA but antagonize CXCR4 migration. Cancer Biology and Therapy. 2013 Feb;14(2):175-183. https://doi.org/10.4161/cbt.22957
Ierano, Caterina ; Basseville, Agnes ; To, Kenneth K W ; Zhan, Zhirong ; Robey, Robert W. ; Wilkerson, Julia ; Bates, Susan E. ; Scala, Stefania. / Histone deacetylase inhibitors induce CXCR4 mRNA but antagonize CXCR4 migration. In: Cancer Biology and Therapy. 2013 ; Vol. 14, No. 2. pp. 175-183.
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