Deciphering the role of LPA and pseudopod machinery during melanoma chemotaxis

Koh, Yvette Wui Hui (2018) Deciphering the role of LPA and pseudopod machinery during melanoma chemotaxis. PhD thesis, University of Glasgow.

Due to Embargo and/or Third Party Copyright restrictions, this thesis is not available in this service.
Printed Thesis Information: https://eleanor.lib.gla.ac.uk/record=b3296268

Abstract

In this thesis, I have applied a complementary and alternative understanding of melanoma chemotaxis by incorporating the role of LPA and through a
pseudopod-centred approach. I have demonstrated that pseudopods are self organising actin entities that undergo mainly bifurcation (splitting) from preexisting protrusions rather than through synthesis of de novo pseudopods for melanoma cell chemotaxis. This observation was also extended to mouse
melanoblast migration in vivo. These superior split pseudopods influence cell
steering by alignment, size and lifetime regulation, and biases retraction. In
non-metastatic cells, they are no longer able to form stable split pseudopods in response to external stimuli. LPA signaling is also established as vital for the stability of split pseudopods. Hence, in the event of LPAR1 perturbation,
metastatic cells formed more actin protrusions but they adopted pseudopod
morphologies similar to the non-metastatic lines. The role of Rac, Ras, Paxillin
and Ezrin in split pseudopod regulation was also explored in this thesis. Finally, the increased stability of split pseudopods acting through LPA signalling could emerge as a signature of metastatic cells.

Item Type: Thesis (PhD)
Qualification Level: Doctoral
Subjects: Q Science > QR Microbiology
Colleges/Schools: College of Medical Veterinary and Life Sciences > Institute of Cancer Sciences > Beatson Institute of Cancer Research
Supervisor's Name: Insall, Professor Robert
Date of Award: 2018
Embargo Date: 22 January 2021
Depositing User: Miss Yvette Koh
Unique ID: glathesis:2018-8686
Copyright: Copyright of this thesis is held by the author.
Date Deposited: 22 Jan 2018 11:01
Last Modified: 20 Feb 2018 09:29
URI: http://theses.gla.ac.uk/id/eprint/8686

Actions (login required)

View Item View Item