White Rose University Consortium logo
University of Leeds logo University of Sheffield logo York University logo

Do myosins contribute to metastasis of prostate cancer cells?

Makowska, Katarzyna Anna (2015) Do myosins contribute to metastasis of prostate cancer cells? PhD thesis, University of Leeds.

[img]
Preview
Text
Makowska_KA_Biological_Sciences_PhD_2015.pdf - Final eThesis - complete (pdf)
Available under License Creative Commons Attribution-Noncommercial-Share Alike 2.0 UK: England & Wales.

Download (8Mb) | Preview

Abstract

Prostate cancer is the second most common cause of death from cancer in men in the UK. Localised disease can be treated with surgery or radiotherapy, but metastasis remains a great therapeutic challenge. Cancer cell migration involves rearrangements of the actin cytoskeleton, which is mediated by its interaction with myosins, a large and diverse family of motor proteins involved in many processes crucial for cell migration, such as cell adhesion, cell polarity or endocytosis. It is likely that the activity of myosins contributes to metastatic spread. I investigated the myosin expression profile in prostate cancer cell lines and found that Myo1b, Myo9b, Myo10 and Myo18a were expressed at higher levels in cells with high metastatic potential. Using an siRNA-based approach, knockdown of each myosin resulted in distinct phenotypes. Myo10 knockdown drastically decreased filopodia of PC3 cells, Myo18a knockdown increased filaments of non-muscle myosin 2A, knockdown of Myo1b and Myo9b increased stress fibre formation. Loss of Myo10 affected cell migration in 2D. In all cases, cell spread area was increased and 3D migration potential was decreased for Myo1b, Myo10 and Myo18a. Myo1b, Myo10 and Myo18a were also expressed in benign prostatic hyperplasia although knockdown of these myosins in benign tissue did not have very clear effects. Glioblastoma cells expressed high levels of Myo10 and showed decreased protrusions after Myo10 knockdown. Taken together, myosins act as molecular motors but also directly influence actin organisation and cell morphology and migration, which can contribute to the metastatic phenotype of cancer cells.

Item Type: Thesis (PhD)
Keywords: Prostate cancer, metastasis, cell migration, myosins
Academic Units: The University of Leeds > Faculty of Biological Sciences (Leeds)
The University of Leeds > Faculty of Biological Sciences (Leeds) > Institute for Molecular and Cellular Biology (Leeds)
Identification Number/EthosID: uk.bl.ethos.675536
Depositing User: Katarzyna Anna Makowska
Date Deposited: 23 Dec 2015 15:15
Last Modified: 26 Apr 2016 15:44
URI: http://etheses.whiterose.ac.uk/id/eprint/11548

Actions (repository staff only: login required)