Receptor Tyrosine Kinase Specificity in Mediating Migration and Induction of Matrix Metalloprotease (MMP)-9 in Keratinocyte and Squamous Cell Carcinoma
Author: Lisa Joy McCawley
Publisher:
Published: 1998
Total Pages: 368
ISBN-13:
DOWNLOAD EBOOKCellular migration is an integral component of normal physiological processes including embryogenesis, angiogenesis, and wound healing. Aberrations in existing mechanisms which dictate epithelial migration can lead to pathological conditions such as tumor metastasis. Receptor tyrosine kinases regulate a many of the cellular events necessary in the development of a migratory phenotype including cell junction dissolution, cell locomotion and matrix remodeling; however, the functional consequences of receptor tyrosine kinase activation display receptor type and cell type specificity. The work described in this thesis addresses selectivity of receptor tyrosine action at several crucial stages required for cell motility and invasion. My research supports a role for selective induction of matrix metalloprotease (MMP)-9 by motogenic receptor tyrosine kinases, and demonstrates that activity of this protease is required during the course of keratinocyte migration, in addition, these studies suggest that duration of MAPK activation is a basis of discrimination between the motogenic and non-motogenic actions of various receptor tyrosine kinases. In this manner, prolonged activation of signaling components provides a mechanism to modulate gene products, such as MMP-9, required during migration, and thus represents an underlying biochemical mechanism for receptor tyrosine kinase specificity in the generation of a migratory phenotype.
