Phospholipase D couples survival and migration signals in stress response of human cancer cells.
MDA-MB-231 human breast cancer cells belong to a highly invasive metastatic cell line that depends on phospholipase D (PLD) activity for survival when deprived of serum growth factors. In response to the stress of serum withdrawal, there is a rapid and dramatic increase in PLD activity. Concomitant with increased PLD activity, there was an increase in the ability of MDA-MB-231 cells to both migrate and invade Matrigel. The ability of MDA-MB-231 cells to both migrate and invade Matrigel was dependent on both PLD and mTOR, a downstream target of PLD signals. Serum withdrawal also led to a PLD-dependent increase in the expression of the stress factor, hypoxia-inducible factor-1alpha. These data reveal that PLD survival signals not only prevent apoptosis but also stimulate cell migration and invasion, linking the ability to suppress apoptosis with the ability to metastasize.
Zheng
Yang
Y
Department of Biological Sciences, Hunter College of the City University of New York, New York, New York 10021, USA.
Rodrik
Vanessa
V
Toschi
Alfredo
A
Shi
Ming
M
Hui
Li
L
Shen
Yingjie
Y
Foster
David A
DA
D045744:Cell Line, Tumor; D002465:Cell Movement; D002470:Cell Survival; D016895:Culture Media, Serum-Free; D006801:Humans; D009362:Neoplasm Metastasis; D018384:Oxidative Stress; D010739:Phospholipase D / Q000378:metabolism*
D016895:Culture Media, Serum-Free; D010739:Phospholipase D