The Effects of RHAMM on Cell Division, Cell Motility, and Tumorigenesis

Overexpression of a RHAMM isoform (RHAMMΔ163) transforms fibroblasts but the mechanisms underlying this oncogenic function are not well understood. RHAMMΔ163 binds to the mitotic spindle and centrosomes via a C-terminal leucine zipper; these interactions are predicted to regulate genomic stability and cell polarity and proposed to account for the oncogenic function of RHAMMΔ163. We hypothesized that RHAMM leucine zipper maintains mitotic spindle integrity and impacts directional cell migration through its interactions with microtubule and centrosome structures. The consequences of a mutated leucine zipper on cell division, cell motility, and tumorigenesis were assessed. Although mutant RHAMMΔ163 promoted polycentrosomy, it did not alter cell cycle progression and did not strongly affect proliferation or tumorigenesis. However, loss of the leucine zipper function blocked directional movement of fibroblasts without affecting rate of motility. These results suggest that the RHAMM leucine zipper selectively regulates directed migration, which is a centrosome function that contributes to tumorigenesis.

Name thesis:degree_name

M Sc

Discipline thesis:degree_discipline

Biochemistry

Grantor dc:publisher

The University of Western Ontario

Year dc:date.issued

2014

Author dc:creator

• Elhayek, Sallie

Advisor dc:contributor.advisor

• Eva Turley

• RHAMM
• leucine zipper
• mitosis
• microtubules
• centrosomes
• cell migration

Language dc:language.iso

en_ca

Handle dc:identifier.uri

https://hdl.handle.net/20.500.14721/35159

OAI identifier oai:identifier

oai:uwo.scholaris.ca:20.500.14721/35159