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J. Biol. Chem., Vol. 281, Issue 23, 15862-15868, June 9, 2006

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Phospholipase D Couples Survival and Migration Signals in Stress Response of Human Cancer Cells^*

From the Department of Biological Sciences, Hunter College of the City University of New York, New York, New York 10021

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^TM. The ability of MDA-MB-231 cells to both migrate and invade Matrigel^TM 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-1. 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.

Received for publication, January 23, 2006 , and in revised form, March 24, 2006.

^* This work was supported by NCI, National Institutes of Health (NIH) Grant CA46677, NIH SCORE Grant GM60654, and Research Centers in Minority Institutions Award RR-03037 from the National Center for Research Resources, NIH. The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

¹ To whom correspondence should be addressed: Dept. of Biological Sciences, Hunter College of the City University of New York, 695 Park Ave., New York, NY 10021. Tel.: 212-772-4075; Fax: 212-772-5227; E-mail: foster{at}genectr.hunter.cuny.edu.

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