| Summary: | Thesis (M.A.) PLEASE NOTE: Boston University Libraries did not receive an Authorization To Manage form for this thesis or dissertation. It is therefore not openly accessible, though it may be available by request. If you are the author or principal advisor of this work and would like to request open access for it, please contact us at open-help@bu.edu. Thank you. === In epithelial cells, formation of stable adherens junction is essential for a number of important cell processes. The central protein responsible for creating cell-cell adhesion is known as E-cadherin. When the lamellipodia of migratory cells make contact, the cell is signaled to send E-cadherin/β-catenin complexes to the point of contact. Upon proper binding of two E-cadherin molecules further E-cadherins are signaled to cluster at the point of contact through cis lateral interactions and a passive diffusion trap mechanism. The actin cytoskeleton is also signaled through Rac1 to interact with the nascent adherens junction. As the adherens junction matures there are further actin cytoskeleton rearrangements and alterations to cell shape due to variable expression of the Rho GTPases. When adhesion in the adherens junction is stable the cell is able to become polarized by the assembly of tight junctions. Interference with any of the steps that lead to the development of a stable, mature, adherens junction results in various disease states such as cancer.
Cancer can develop in epithelial cells due to E-cadherin dysfunction, particularly gastric, breast, ovarian, head and neck, and prostate cancer are seen. E-cadherin dysfunction can be caused by interference with proper transcription, N-glycosylation, and recycling. Transcription is most commonly disrupted due to acetylation of the E-cadherin promoter by improperly modulated transcriptional repressor, such as Snail. Aberrant Nglycosylation and/or modification with branching β1, 6 GlcNAc can interfere with the creation of stable adherens junction by interfering with E-cadherin binding. Increased endocytosis of E-cadherin via irregular Rho GTPase activity destabilizes adherens junctions. These interferences effect an epithelial to mesenchymal transition that can act as a metastatic cancer phenotype.
E-cadherin serves a crucial function in cell-cell adhesion and preventing cells from exhibiting malignancy. It has been shown that restoration of its function in cancer cell lines reduces the invasiveness of cancer cells and returns to the cell to a normal epithelial phenotype. Knowledge of E-cadherin, its regulators, and association with the actin cytoskeleton will undoubtedly have clinical impacts in cancer treatment. However, understanding of E-cadherin is still incomplete, in particularly more studies need to be done in the area of Rho GTPases and N-glycosylation, There has also been recent controversy in identifying the principal molecule that links the actin cytoskeleton and α- catenin to mediate the binding of the E-cadherin/β-catenin complex to actin. === 2031-01-01
|
|---|
