The CD151-α3β1 axis and its role in breast cancer progression

Baldwin, Gouri Seetharaman (2012). The CD151-α3β1 axis and its role in breast cancer progression. University of Birmingham. Ph.D.

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Abstract

This thesis investigates the role of CD151 in modulating the form and function of its integrin partners, α3β1 and α6β1/β4. Stable depletion of CD151 in the MDA-MB-231 (MDA-231) cell line, changed the glycosylation profile of α3β1, but not α6β1/β4 integrins. Glycosylation of CD151, tight association between CD151 and α3β1 integrin and recruitment into tetraspanin enriched microdomains (TERM) are all required for this effect and the intervention occurs during the first mannose trimming step within the ER. Further analysis showed that CD151 preferentially associates with α3β1 over α6β1/β4. CD151 mediated changes to glycosylation of α3β1 integrin decreased their ability to migrate towards Lm332 by ~90%. Sucrose density gradient assays showed α3β1 and α6β1/β4 are recruited by CD151 into the light fractions as part of a TERM as well as separate entities. Glyco-analysis of the tetraspanins themselves showed CD9 and possibly CD63 and CD82 to be phospho-mannosylated. Castanospermine treatment dramatically reduced the level of CD151, α3β1 and α6β1/β4 in these cells, indicating a novel therapeutic use. Depletion of various tetraspanins in MDA-231 altered their cell surface glycotope presentation and the cleavage profile of α6β1/β4 integrin; highlighting the role played by tetraspanins in post-translational modification of their partners.

Type of Work:

Thesis (Doctorates > Ph.D.)

Award Type:

Doctorates > Ph.D.

Supervisor(s):