Adhesion-Dependent Regulation of Cell Growth and Apoptosis in Human Breast Cancer
Final rept. 1 Jul 1999-1 Jul 2002
COLD SPRING HARBOR LAB OF QUANTITATIVE BIOLOGY NY
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We have studied the role of the actin cytoskeleton and myosin II in adhesion-dependent signaling and regulation of apoptosis in normal and transformed epithelial cells. Normal epithelial cells require attachment to the extracellular matrix ECM for survival, and disruption of cell-ECM interactions results in induction of apoptosis, a phenomenon termed anoikis. By contrast, transformed cells do not require interaction with the ECM and do not undergo apoptosis when grown in suspension. This property plays a critical role in the ability of cancerous cells to metastasize. We have found that activation of myosin II is a critical step in the generation of signals that prevent programmed cell death. In addition, these studies show that transformed epithelial escape apoptosis due to constitutive activation of signaling pathways dependent on myosin II. We have identified key-signaling pathways that are altered in transformed cells and thereby contribute to the ability of tumor cells to escape anoikis. Collectively these studies provide important new information regarding specific pathways that regulate myosin II and identify potential therapeutic targets for the treatment of breast cancer, as well as other cancers.
- Medicine and Medical Research