Image-based phenotypic screening for breast cancer metastasis drug target discovery

Author(s):
Fokkelman, M.
Published
2017
Publication type
Doctoral Thesis

Abstract

The main aim of this thesis was to unravel the signaling

and regulatory networks that drive tumor cell migration during breast cancer

metastasis. Understanding how tumor cells migrate, how this process is

differentially regulated, and how this highly heterogeneous and plastic behavior is coordinated during metastatic dissemination, will ultimately provide novel insights in therapeutic opportunities. The work presented in this thesis includes different microscopy techniques and analytical tools to study migratory behavior (Chapters 2, 3, 4, and 5), reveals an important role for adhesion GPCRs in cell adhesion and migration (Chapter 3), provides a compendium of genes that drive tumor cell migration in breast cancer (Chapter 4), and investigates the intricate connection between adhesion dynamics, cell migration and contractility (Chapter 5). Collectively, this work provides novel insights in the molecular determinants of tumor cell migration and will help us better understand the signaling landscape that drives the formation of breast cancer metastases.

Cell_migrationCell_adhesionFocal_adhesionBreast_cancerRNAi_screenMetastasis microscopy
Defense date
2017-11-22
Language
English
Supervisor(s)
Water, B. van der
Committee member(s)
Irth, H.; Bouwstra, J.A.; IJzerman, A.P.; Smit, M.J.; Rheenen, J. van; Sonnenberg, A.
Qualification
Ph.D.
Degree granting institution
Leiden Academic Centre for Drug Research (LACDR), Science, Leiden University, Leiden
hdl
1887/57506
ISBN(s)
9789402808360

Funding

Sponsorship
Systems Microscopy Network of Excellence Charles River Laboratories