Targeting choline phospholipid metabolism: GDPD5 and GDPD6 silencing decrease breast cancer cell proliferation, migration, and invasion

NMR Biomed. 2016 Aug;29(8):1098-107. doi: 10.1002/nbm.3573. Epub 2016 Jun 30.


Abnormal choline phospholipid metabolism is associated with oncogenesis and tumor progression. We have investigated the effects of targeting choline phospholipid metabolism by silencing two glycerophosphodiesterase genes, GDPD5 and GDPD6, using small interfering RNA (siRNA) in two breast cancer cell lines, MCF-7 and MDA-MB-231. Treatment with GDPD5 and GDPD6 siRNA resulted in significant increases in glycerophosphocholine (GPC) levels, and no change in the levels of phosphocholine or free choline, which further supports their role as GPC-specific regulators in breast cancer. The GPC levels were increased more than twofold during GDPD6 silencing, and marginally increased during GDPD5 silencing. DNA laddering was negative in both cell lines treated with GDPD5 and GDPD6 siRNA, indicating absence of apoptosis. Treatment with GDPD5 siRNA caused a decrease in cell viability in MCF-7 cells, while GDPD6 siRNA treatment had no effect on cell viability in either cell line. Decreased cell migration and invasion were observed in MDA-MB-231 cells treated with GDPD5 or GDPD6 siRNA, where a more pronounced reduction in cell migration and invasion was observed under GDPD5 siRNA treatment as compared with GDPD6 siRNA treatment. In conclusion, GDPD6 silencing increased the GPC levels in breast cancer cells more profoundly than GDPD5 silencing, while the effects of GDPD5 silencing on cell viability/proliferation, migration, and invasion were more severe than those of GDPD6 silencing. Our results suggest that silencing GDPD5 and GDPD6 alone or in combination may have potential as a new molecular targeting strategy for breast cancer treatment. Copyright © 2016 John Wiley & Sons, Ltd.

Keywords: GDPD5; GDPD6; breast cancer; choline phospholipid metabolism; gene targeted treatment.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Breast Neoplasms / metabolism*
  • Breast Neoplasms / pathology
  • Breast Neoplasms / therapy*
  • Cell Line, Tumor
  • Cell Movement
  • Cell Proliferation
  • Gene Silencing
  • Genetic Therapy / methods*
  • Glycerylphosphorylcholine / metabolism*
  • Humans
  • MCF-7 Cells
  • Molecular Targeted Therapy / methods*
  • Neoplasm Invasiveness
  • Phospholipases / metabolism*
  • RNA, Small Interfering / administration & dosage
  • Treatment Outcome


  • RNA, Small Interfering
  • Glycerylphosphorylcholine
  • GPCPD1 protein, human
  • Phospholipases