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Cover Page

The handle http://hdl.handle.net/1887/92349 holds various files of this Leiden University dissertation.

Author: Liu, S.

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TGFβ signaling

in cancer progression

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ISBN:978-94-028-2053-9

© 2020, Sijia Liu, Leiden, the Netherlands. All rights reserved. No part of this thesis may be reproduced, stored, translated or transmitted in any form or by any means now or hereafter, electronic or mechanical without prior written permission from the author.

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TGFβ signaling

in cancer progression

Proefschrift

ter verkrijging van

de graad van Doctor aan de Universiteit Leiden,

op gezag van Rector Magnificus prof.mr. C.J.J.M. Stolker,

volgens besluit van het College voor Promoties

te verdedigen op donderdag 28 mei 2020

klokke 16:15 uur

door

Sijia Liu

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Promotor: Prof. Dr. P. ten Dijke Co-promotor: Dr. P.P. Geurink Leden promotiecommissie:

Prof. Dr. T.K. Sixma (Netherlands Cancer Institute) Prof. Dr. A. Moustakas (Uppsala University) Prof. Dr. A.C.O. Vertegaal

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Contents

7

13

35

51

79

105

129

137

139

141

143

145

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Chapter 1

General introduction

Chapter 2

Regulation of TGFβ pathway by deubiquitinases in cancer

Chapter3

Invasive behavior of human breast cancer cells in embryonic zebrafish

Chapter 4

Deubiquitinase activity profiling identifies UCHL1 as a candidate

oncoprotein that promotes TGFβ-induced breast cancer metastasis

Chapter 5

A small-molecule activity-based probe for monitoring

UCHL1 activity in live cells and zebrafish embryos

Chapter 6

Mutational activation of BRAF confers sensitivity

to TGFβ inhibitors in human cancer cells

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