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.

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 > School of Cancer Sciences > Beatson Institute of Cancer Research
• Supervisor's Name: Insall, Professor Robert
• Date of Award: 2018
• Embargo Date: 22 January 2022
• 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: 26 Jan 2024 14:31
• Thesis DOI: 10.5525/gla.thesis.8686
• URI: https://theses.gla.ac.uk/id/eprint/8686