The Importance of Autophagy in Breast Cancer Development and Treatment
Annual rept. 6 Feb 2009-5 Feb 2010
PENNSYLVANIA STATE UNIV HERSHEY
Pagination or Media Count:
During this grant period, we found that growth factor inhibitors as well as nutrient depletion activated autophagy in human beast cancer cells, and the increased activity of autophagy was associated with a decrease in cellular ATP and an increase in activities of AMP kinase and eEF-2 kinase. Silencing of eEF-2 kinase relieved the inhibition of protein synthesis, led to a greater reduction of cellular ATP, and blunted autophagic response. We further demonstrated that suppression of eEF-2 kinase-regulated autophagy impeded cell growth in serumnutrient-deprived cultures and handicapped cell survival, and enhanced the efficacy of the growth factor inhibitors such as trastuzumab, gefitinib, and lapatinib. The results of this study provide new evidence that activation of eEF 2 kinase-mediated autophagy plays a protective role for cancer cells under metabolic stress conditions, and that targeting autophagic survival may represent a novel approach to enhancing the effectiveness of growth factor inhibitors such as trastuzumab, gefitinib, and lapatinib .
- Medicine and Medical Research