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University of Groningen

CRISPR/Cas9 and targeted cancer therapy

Liu, Bin

DOI:

10.33612/diss.99103461

IMPORTANT NOTE: You are advised to consult the publisher's version (publisher's PDF) if you wish to cite from

it. Please check the document version below.

Document Version

Publisher's PDF, also known as Version of record

Publication date:

2019

Link to publication in University of Groningen/UMCG research database

Citation for published version (APA):

Liu, B. (2019). CRISPR/Cas9 and targeted cancer therapy. University of Groningen.

https://doi.org/10.33612/diss.99103461

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Downloaded from the University of Groningen/UMCG research database (Pure): http://www.rug.nl/research/portal. For technical reasons the number of authors shown on this cover page is limited to 10 maximum.

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CRISPR/Cas9 and targeted cancer

therapy

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The research described in this thesis was carried out at the department of Chemical and Pharmcetical Biology at the University of Groningen.

The research was crried out according to the rquirements of the Graduate School of Science, Faculty of Science and Engineering, University of Groningen, The Netehrlands

Printing of this thesis was financially supported by the University Library and the Graduate School of Science, University of Groningen, The Netherlands.

Printing: Ridderprint BV | www.ridderprint.nl

IBSN (ebook): 978-94-6375-611-2 IBSN (printed version): 978-94-6375-610-5

Copyright © 2019 Bin Liu. All rights are reserved. No part of this thesis may be reproduced or transmitted in any form or by any means without the prior permission in writing of the author.

CRISPR/Cas9 and targeted cancer

therapy

PhD thesis

to obtain the degree of PhD at the University of Groningen

on the authority of the Rector Magnificus Prof. C. Wijmenga

and in accordance with the decision by the College of Deans. This thesis will be defended in public on Tuesday 29 October 2019 at 11.00 hours

by

Bin Liu

born on 16 February 1989 in Jiangsu, China

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The research described in this thesis was carried out at the department of Chemical and Pharmcetical Biology at the University of Groningen.

The research was crried out according to the rquirements of the Graduate School of Science, Faculty of Science and Engineering, University of Groningen, The Netehrlands

Printing of this thesis was financially supported by the University Library and the Graduate School of Science, University of Groningen, The Netherlands.

IBSN (ebook): 978-94-6375-611-2 IBSN (printed version): 978-94-6375-610-5

Copyright © 2019 Bin Liu. All rights are reserved. No part of this thesis may be reproduced or transmitted in any form or by any means without the prior permission in writing of the author.

CRISPR/Cas9 and targeted cancer

therapy

PhD thesis

to obtain the degree of PhD at the University of Groningen

on the authority of the Rector Magnificus Prof. C. Wijmenga

and in accordance with the decision by the College of Deans. This thesis will be defended in public on Tuesday 29 October 2019 at 11.00 hours

by

Bin Liu

born on 16 February 1989 in Jiangsu, China

(5)

Supervisors

Prof. H.J. Haisma Prof. F.J. Dekker

Assessment Committee

Prof. M. Schmidt

Prof. V.W. van Beusechem Prof. F. Foijer

Contents

Chapter 1 Scope and outline of this thesis ... 7 Chapter 2 CRISPR/Cas9: A powerful tool for identification of new targets for cancer treatment... 17 Chapter 3 CRISPR/Cas9 for overcoming drug resistance in solid tumors... 75 Chapter 4 Transcriptional activation of cyclin D1 via HER2/HER3 contributes to cell survival and

tyrosine kinase inhibitor resistance in non-small cell lung carcinoma ... 101 Chapter 5 CX Chemokine Receptor 7 Contributes to Survival of KRAS-Mutant Non-Small Cell Lung

Cancer upon Loss of Epidermal Growth Factor Receptor... 135 Chapter 6 CRISPR-mediated ablation of overexpressed EGFR in combination with sunitinib significantly suppresses renal cell carcinoma proliferation ... 171 Chapter 7 Inhibition of Histone deacetylase 1 (HDAC1) and HDAC2 enhances CRISPR/Cas9 genome

editing ... 195 Chapter 8 Summary and Future Perspectives ... 236

Appendices Acknowledgement List of publication About the author

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Supervisors

Prof. H.J. Haisma Prof. F.J. Dekker

Assessment Committee

Prof. M. Schmidt

Prof. V.W. van Beusechem Prof. F. Foijer

Contents

Chapter 1 Scope and outline of this thesis ... 7 Chapter 2 CRISPR/Cas9: A powerful tool for identification of new targets for cancer treatment ... 17 Chapter 3 CRISPR/Cas9 for overcoming drug resistance in solid tumors ... 75 Chapter 4 Transcriptional activation of cyclin D1 via HER2/HER3 contributes to cell survival and

tyrosine kinase inhibitor resistance in non-small cell lung carcinoma ... 101 Chapter 5 CX Chemokine Receptor 7 Contributes to Survival of KRAS-Mutant Non-Small Cell Lung

Cancer upon Loss of Epidermal Growth Factor Receptor ... 135 Chapter 6 CRISPR-mediated ablation of overexpressed EGFR in combination with sunitinib significantly suppresses renal cell carcinoma proliferation ... 171 Chapter 7 Inhibition of Histone deacetylase 1 (HDAC1) and HDAC2 enhances CRISPR/Cas9 genome

editing ... 195 Chapter 8 Summary and Future Perspectives ... 236

Appendices Acknowledgement List of publication About the author

(7)

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