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DNA damage signaling networks: from stem cells to cancer

Carreras Puigvert, J.

Citation

Carreras Puigvert, J. (2011, October 20). DNA damage signaling networks:

from stem cells to cancer. Retrieved from https://hdl.handle.net/1887/17980

Version: Corrected Publisher’s Version

License: Licence agreement concerning inclusion of doctoral thesis in the Institutional Repository of the University of Leiden

Downloaded from: https://hdl.handle.net/1887/17980

Note: To cite this publication please use the final published version (if applicable).

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DNA damage signaling networks:

from stem cells to cancer

Jordi Carreras Puigvert

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DNA damage signaling networks: from stem cells to cancer Jordi Carreras Puigvert

October 2011

Cover: HepG2 cell with Annexin V staining, by Lisa Fredriksson and Bram Herpers.

Printed by Wöhrmann Print Service, Zutphen, The Netherlands ISBN: 978-90-8570-427-0

2011, Jordi Carreras Puigvert. All rigths reserved. No part of this thesis my be reproduced or transmitted in any form, by any means, electronic or mechanical, without prior written permission of the author.

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DNA damage signaling networks:

from stem cells to cancer

Proefschrift ter verkrijging van

de graad van Doctor aan de Universiteit van Leiden, op gezag van Rector Magnificus prof. mr. P.F. van der Heijden,

volgens besluit van het College voor Promoties te verdedigen op donderdag 20 Oktober 2011

klokke 16.15 uur

door

Jordi Carreras Puigvert geboren te La Roca del Vallès

in 1978

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Promotion Committee

Promotor:

Prof. Dr . B. van de Water LACDR, Leiden

Co-promotor:

Dr. E.H.J. Danen LACDR, Leiden

Overige leden:

Prof. Dr. J. Kuiper LACDR, Leiden Prof. Dr. J. Brouwer LACDR, Leiden Prof. Dr. M. Danhof LACDR, Leiden Prof. Dr. L.H.F. Mullenders LUMC, Leiden

Prof. Dr. G.T.J. van der Horst Erasmus MC, Rotterdam Dr. W. Vermeulen Erasmus MC, Rotterdam Prof. Dr. H.P.J. Te Riele NKI, Amsterdam

The investigations described in this thesis were performed at the Division of Toxicology of the Leiden/Amsterdam Center for Drug Research, Leiden University, Leiden, The Netherlands.

The printing of this thesis was financially supported by:

Leiden/Amsterdam Center for Drug Research J.E. Jurriaanse Stichting.

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A la meva mare

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Table of contents

Chapter 1 9 General introduction and scope of this thesis.

Chapter 2 27 The cancer stem cell microenvironment and anti-cancer therapy.

International Journal of Radiation Biology

Chapter 3 37 High throughput live cell imaging of apoptosis.

Current Protocols in Cell Biology

Chapter 4 53 Global phosphoproteome profiling reveals unanticipated

networks responsive to cisplatin treatment of embryonic stem cells.

Molecular and Cellular Biology, under revision

Chapter 5 87 Mapping DNA damage response signaling networks in ES

cells - downregulation of CSNK1a1 leads to enhanced Wnt signaling that acts as a brake on p53-mediated apoptosis.

Manuscript in preparation

Chapter 6 117 Integrins and oncogenes: partners in crime.

Molecular and Cellular Pharmacology

Chapter 7 125 Cross-talk between integrins and oncogenes modulates chemosensitivity.

Molecular Pharmacology

Chapter 8 137 Summary and discussion

Appendix:

Nederlandse samenvatting 147

Resum en Català 153

Curriculum vitae 157

List of publications 159

Acknowledgments 161

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