University of Groningen
Molecular mechanisms regulating epithelial-to-mesenchymal transition and therapy sensitivity
in breast cancer and glioblastoma
Liang, Yuanke
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Publication date: 2019
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Liang, Y. (2019). Molecular mechanisms regulating epithelial-to-mesenchymal transition and therapy sensitivity in breast cancer and glioblastoma. Rijksuniversiteit Groningen.
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Molecular mechanisms regulating
epithelial-to-mesenchymal transition
and therapy sensitivity in breast cancer
and glioblastoma
Liang, Y
Molecular mechanisms regulating epithelial-to-mesenchymal transition and therapy sensitivity in breast cancer and glioblastoma
Thesis, University of Groningen, Groningen, The Netherlands
Printing of this thesis was financially supported by the University of Groninge, the Graduate School of Medical Sciences and the Stichting Werkgroep Interne Oncologie, UMCG.
Front cover: The background image shows immunofluorescent staining of fibronectin (purple) and nuclei (yellow) of U87 cells cultured in 3D matrigel model.
Back cover: Confocal microscope 3D image of GSC23 GFP+ (upper panel) and GSC23-CD146-ko GFP+ (lower panel) glioblastoma cells infiltrating the brain organoid.
Cover: Yuanke Liang and Yang Wu Layout: Yuanke Liang
Printed by: Ridderprint ISBN: 978-94-034-1752-3 ISBN (digital): 978-94-034-1751-6 © 2019, Y Liang
All rights reserved. No part of this thesis may be reproduced, stored in a retrieval system, or transmitted in any form or by any means, mechanically, by photocopying, recording, or otherwise, without prior written permission of the author.
Molecular mechanisms regulating epithelial-to-
mesenchymal transition and therapy sensitivity
in breast cancer and glioblastoma
PhD thesis
to obtain the degree of PhD at the
University of Groningen
on the authority of the
prof. dr. E. Sterken
and in accordance with
the decision by the College of Deans.
This thesis will be defended in public on
Tuesday 18 June 2019 at 11:00 hours
by
Yuanke Liang
born on 25 February 1988
Supervisors
Prof. dr. F.A.E. Kruyt
Prof. dr. Guojun Zhang
Co-supervisor
Dr. W.F.A. den Dunnen
Assessment Committee
Prof. dr. M.A.T.M. van Vugt
Prof. dr. H. Hollema
Dedicated to My Wife Xiaoling and
Daughter Yanzhi
Paranymphs
Margot de Looff
Yi Yu
CONTENTS
Chapter 1 General introduction and outline of the thesis 9
Chapter 2 MCAM/CD146 promotes tamoxifen resistance in breast cancer cells through induction of epithelial -mesenchymal transition, decreased ERα expression and AKT activation.
Cancer Lett. 2017 Feb 1;386:65-76
27
Chapter 3 Notch3 maintains luminal phenotype and suppresses tumorigenesis and metastasis of breast cancer via trans-activating estrogen receptor-α
Theranostics. 2017 Sep 20;7(16):4041-4056
51
Chapter 4 MiR-221/222 promote epithelial-mesenchymal transi-tion by targeting Notch3 in breast cancer cell lines
NPJ Breast Cancer. 2018 Aug 6;4:20
79
Chapter 5 Notch3 inhibits epithelial–mesenchymal transition in breast cancer via a novel mechanism, upregulation of GATA-3 expression
Oncogenesis. 2018 Aug 13;7(8):59
95
Chapter 6 Inhibition of Notch1 reverses EMT and chemoresis-tance to cisplatin via direct down-regulation of MCAM in triple-negative breast cancer cells
Submitted
127
Chapter 7 CD146/MCAM regulates mesenchymal properties, stemness, radio-resistance and YAP activity in glio-blastoma
Manuscript in preparation
159
Chapter 8 Summary, discussion and future perspectives 185
Chapter 9 Summary in Chinese (中文总结与展望) 201
Chapter 10 Summary in Dutch (Nederlandse samenvatting) 209 Appendices
Curriculum vitae, List of publication, Acknowledge-ments
