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Norepinephrine, epinephrine protect cells from anoikis by activating focal adhesion kinase

-- Rick Ansorge

Friday, April 23, 2010 (Last Updated: 04/26/2010)

FRIDAY, April 23 (HealthDay News) -- In patients with ovarian cancer, focal adhesion kinase (FAK) modulation by stress hormones -- especially norepinephrine and epinephrine -- may contribute to tumor progression, according to research published online April 12 in the Journal of Clinical Investigation.

Anil K. Sood, M.D., of the University of Texas M.D. Anderson Cancer Center in Houston, and colleagues studied human ovarian cancer cells which were exposed to either norepinephrine or epinephrine, and mice with a model of human ovarian cancer which were subjected to restraint stress. They also examined 80 cases of invasive epithelial ovarian cancer to assess the role of stress-induced FAK activity.

The researchers found that cancer cells exposed to the hormones exhibited lower levels of anoikis. In the mice, they found that the associated increases in norepinephrine and epinephrine protected the tumor cells from anoikis and promoted their growth by binding with the β2-adrenergic receptor and activating FAK. In the human cases, they found that 67 percent had increased FAK expression and that 50 percent had heightened levels of phosphorylated FAK. Three-year survival was significantly lower in those with increased FAK expression or heightened levels of phosphorylated FAK (30 and 15 percent, respectively) than in those with low FAK expression (65 percent).

"These findings also imply that the neuroendocrine 'macroenvironment' may play a significant role in shaping cellular activity in the tumor microenvironment in ways that ultimately facilitate cancer progression," the authors write. "Thus, protective interventions targeting the neuroendocrine system might simultaneously modulate multiple molecular pathways involved in tumor metastasis (e.g., anoikis, angiogenesis, and invasion)."

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Specialties Hematology & Oncology
Urology
Surgery
Radiology
Family Practice

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