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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Curriculum vitae
Publications
216
Curricum vitae
Curriculum vitae
Personal
Name Yuanke Liang
Date and place of Birth 25 February 1988, Guangdong, China Personal email address ykliang12345@163.com
Education
2015-current PhD student at University of Groningen, The Netherlands. (Supervisors: Prof. dr. Frank A.E. Kruyt; Prof. dr. Guojun Zhang; Prof. dr. W.F.A. (Wilfred) den Dunnen)
2012-2015 Master of Medicine, Shantou University Medical College, China (Supervisor: Prof. Guo-Jun Zhang)
2007-2012 Bachelor of Medicine, Shantou University Medical College, China
Research interests Exploring molecular mechanisms of tumor aggressiveness, therapuetic resistance.
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PUBLICATIONS
Publication (* contribute equally)
1. Yuan-Ke Liang*, De Zeng*, Ying-Sheng Xiao, Yang Wu, Yan-Xiu Ouyang, Min Chen, Yao-Chen Li, Hao-Yu Lin, Xiao-Long Wei, Yong-Qu Zhang, Frank A.E. Kruyt, Guo-Jun Zhang. 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
2. Xiao-Wei Dou*, Yuan-Ke Liang*, Hao-Yu Lin, Xiao-Long Wei, Yong-Qu Zhang, Jing-Wen Bai, Chun-Fa Chen, Min Chen, Cai-Jing-Wen Du, Yao-Chen Li, Jie Tian, Kwan Man and Guo-Jun Zhang. Notch3 maintains luminal phenotype and suppresses tumor-igenesis and metastasis of breast cancer via trans-activating estrogen receptor-α. Theranostics. 2017 Sep 20;7(16):4041-4056
3. Yuan-Ke Liang*, Haoyu Lin*, Chunfa Chen,De Zeng. Prognostic values of distinct CBX family members in breast cancer. Oncotarget. 2017 Sep 28;8(54):92375-92387 4. Yuan-Ke Liang*, Hao-Yu Lin*, Xiao-Wei Dou, Min Chen, Xiao-Long Wei, Yong-Qu Zhang, Yang Wu, Chun-Fa Chen, Jing-Wen Bai, Ying-Sheng Xiao , Yu-Zhu Qi, Frank A.E. Kruyt and Guo-Jun Zhang. MiR-221/222 promote epithelial-mesenchymal transition by targeting Notch3 in breast cancer cell lines. NPJ Breast Cancer. 2018 Aug 6;4:20
5. Hao-Yu Lin, Yuan-Ke Liang, Xiao-Wei Dou, Chun-Fa Chen, Xiao-Long Wei, De Zeng, Jing-Wen Bai, Yu-Xian Guo, Fang-Fang Lin, Wen-He Huang, Cai-Wen Du, Yao-Chen Li, Min Chen & Guo-Jun. Notch3 inhibits epithelial–mesenchymal transition in breast cancer via a novel mechanism, upregulation of GATA-3 expression. Onco-genesis. 2018 Aug 13;7(8):59
6. Ying-Sheng Xiao, De Zeng, Yuan-Ke Liang, Yang Wu, Mei-Fang Li, Yu-Zhu Qi, Xiao-Long Wei, Wen-He Huang, Min Chen, Guo-Jun Zhang. Major vault protein is a direct target of Notch1 signaling and contributes to chemoresistance in triple-negative breast cancer cells. Cancer Lett. 2019 Jan;440-441:156-167
7. Hao-Yu Lin, De Zeng Yuan-Ke Liang, Xiao-Long Wie, Chun-Fa Chen. GATA3 and TRPS1 are distinct biomarkers and prognostic factors in breast cancer: Database mining for GATA family members in malignancies. Oncotarget. 2017 May 23;8(21):34750-34761
8. Chen CF, Dou XW, Liang YK, Lin HY, Bai JW, Zhang XX, Wei XL, Li YC, Zhang GJ. Notch3 overexpression causes arrest of cell cycle progression by inducing Cdh1 expression in human breast cancer cells. Cell Cycle. 2016;15(3):432-40
9. Yong-Qu Zhang, Xiao-Long Wei, Yuan-Ke Liang, Wei-Ling Chen, Fan Zhang, Jing-WenBai, Si-Qi Qiu, Cai-WenDu, Wen-He Huang*, Guo-Jun Zhang*. Over-Ex-pressed Twist Associates with Markers of Epithelial Mesenchymal Transition and Predicts Poor Prognosis in Breast Cancers via ERK and Akt Activation. PLoS One. 2015 Aug 21;10(8)
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Dankwoord (acknowledgements)
When I started to write this part of my thesis, the past 4-years Ph.D. journey reappeared in my mind. It evoked me all the wonderful moments I experienced and the extremely kind people I met. Pursuing this Ph.D. has been a truly life-changing experience for me and this thesis would not be accomplished without support and guidance that I received from nu-merous people. Although it is only my name on the thesis’s cover, many people have con-tributed to my Ph.D. in their own particular way and for that I would like to give them special thanks.
First and foremost, I would like to offer my sincerest gratitude to my supervisors Prof. dr.
Frank A.E. Kruyt, Prof. dr. Guojun Zhang and co-supervisor Prof. dr. W.F.A. (Wilfred) den Dunnen. Dear Frank, I am very grateful that you provided me this wonderful opportunity to
study my PhD in your group. I still remember how nervous I felt in our first Skype interview 4 years ago, however, when you pronounced my name Yuanke as “Yongki” at the beginning of conversation, I could not disguise my amusement at that moment, and miraculously I didn’t feel nervous anymore. The first interview proceeded very well, since then you called me Kevin every time. You rarely missed our regular weekly meeting. Sometimes I don’t have so much new data to discuss for 1 hour, but we still can talk about the Dutch weather. After the meeting, you usually gave me some inspiring words and motivated me to keep my spirit high and proceed. You taught me how to make presentation, how to design the experiment, and what impressed me most was you said to me that “If you have any question, please send me an e-mail or just come to knock on my door anytime”. You didn’t encourage me keep working in the weekend, though Win Sen and me usually arrange some experiments in the weekend. You said to me that working hard during working hours is great but don’t forget to enjoy the live in the Netherlands. I am very grateful that you put a lot of effort into my thesis writing. Without your enthusiasm, encouragement, support and continuous optimism this thesis would hardly have been completed.
I would like to pay special appreciation to my supervisor Prof. Zhang. Dear Prof. Zhang, I still remember the first time I met you in the class in 2010 when you gave us a lesson on breast cancer. You have a very high reputation among our students, so I have no hesitation to send my application to you to be supervisor in Master degree of medicine. How lucky that I past the examination and interview and became your student. You led me to the gate of medical research and encourage me keep going and find my own interest. Your mix of straightfor-ward criticism combined with heart-warming support have made me realize that I am only a novice in this exciting profession , and at the same time gave me great confidence and en-couragement to lucubrate into our research. In addition, you usually share your experience of studying and working in Japan and USA with me and encourage me to pursuit the Ph.D. abroad to broaden my horizon. What impressed me most was that you advised me to be more of a scientist than a doctor and insisted on doing research in my future career. I am really grateful for having you as supervisor.
My sincere thanks also goes to my co-supervisor Prof. dr. W.F.A. (Wilfred) den Dunnen. Dear
Wilfred, when the first time I met you in Pathology department, you gave me the impression
that you are an elegant gentleman and very sagacious and amiable. I know you are very busy, however, you always do your best to squeeze time in your schedule to have a meeting with me and I really appreciate that. You are very professional at Pathology and teach me a lot in this academic field. You usually advise me that “Don’t rush to do the experiment; To think about what is your scientific question?”. I totally agree with you and I really hope to be a scientist soon, and able to ask the best “scientific question”.
I would like to express my deep gratitude to Coby and Hetty. Dear Coby and Hetty, I partic-ularly grateful for your kind help during my PhD study in Groningen. I am very inspired by
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your enthusiasm, meticulousness and persistence for scientific research. I cannot forget the valuable conversation and suggestions you gave in my presentations on Tuesday meeting. In addition, I am so happy that both of you enjoy the Chinese tea ceremony.
My sincere thanks also goes to Prof. dr. Steven de Jong and Prof. dr. Marcel van Vugt. Dear Steven and Marcel, thanks for hosting the Tuesday journal club and Friday oncology research meeting. I know that both of you spend a lot of attentions for the meeting. In ad-dition to my own field of research, I also learned a lot from various of lectures which really help me to broaden my research horizon.
I would also like to extend my acknowledgements to reading committee members, Prof. dr.
Marcel van Vugt, Prof. dr. Harry. Hollema, and Prof. dr. Marc Vooijs. Thanks for taking your
precious time for evaluating my thesis.
My special thanks are extended to our group members, Win Sen, Natalia, Margot, Nadia,
Bianca and Justin. Dear Win Sen, your enthusiasm, passion and hardworking on the
scien-tific research really impressed me. I am grateful that you encouraged me and helped me to improve my English. Escaping Groningen to travel around in the Netherlands with you was great fun. Dear Natalia, it’s my honor to work with you in glioblastoma investigations. I was a totally novice in glioblastoma research when I came here, however, you taught me how to culture glioblastoma neurosphere and answered my questions patiently and I really appre-ciated that. I still remember we, together with Win Sen, went to EACR in Amsterdam and had a good times. Dear Margot, it’s my honor to know you and be your colleague. Thanks for giving me so many helpful suggestions when I presented on our Tuesday meetings. I am so happy and appreciate that you will be one of my paranymphs. I would like to thank my mas-ter student Nadia who is inmas-terested in glioblastoma research. Dear Nadia, you are a smart, diligent, and modest person and I really enjoyed working with you. I hope you will get your MD/PhD offer soon and have great success in your research. Dear Bianca, your enthusiasm and optimistic attitude toward work and life left me with a deep impression. I hope you will be an excellent Neurosurgeon as you wish. Dear Justin, I read your thesis over and over again even though I haven’t met you face to face until now, I learn a lot from your thesis and thanks for helping me performing the CAM assay in Sweden.
Studying and working in the MOL lab has been great. I particularly would like to express my sincere appreciation for my dear colleagues: Shang Li, Thijs, Gerda, Ximena, Joost, Bea,
Siqi, Qiu, Na Li, Jie Ma, Rolf, Yannick, Sergi, Carlos, Colin, Jiske, Linda, Danique, Francien, Frans, Arko, Arjan, Nathalie, and Vivian. Dear Thijs, Gerda, Ximena, and Joost, we had
fan-tastic day in Shang’s home. We learned how to make Chinese dumplings and I was so sur-prised that all of you mastered the skill so fast and even optimized the protocol.
I’m deeply grateful to all the co-authors and collaborators who contributed to this thesis.
Xiaowei Dou, Xiaolong Wei, Min Chen, Haoyu Lin, De Zeng, Wenxiu Ni, Yongqu Zhang, Jingwen Bai, Chunfa Chen, Xiaofen Wen, Jiaxin Shen, Yuxian Guo, Weiling Chen, Yang Wu, Yingsheng Xiao, Zun Wang, Minna Chen, Cuiping Guo, Didi Xi, Ronghui Li, Lifang He and Xiangrong Luo. Dear Dr. Xiaowei Dou, you were my daily supervisor when I was in
Chang-jiang Scholar’s lab, thank you for teaching me so many experimental techniques. When I failed in the experiment, you helped me to analyze the reasons patiently and encouraged me to keep trying. When I had some exciting findings, you were happier than anyone else. I feel so lucky that I know such a nice colleague like you. Dear Prof. Min Chen, I am particularly grateful for your advices, guidance, and discussions in my projects. Dear Dr. Xiaolong Wei, I am apprecite that you gave so many good suggestions and support to my study and daily life when I was studying in Shantou. Dear Dr. Haoyu and Dr. Yongqu, the atmosphere is always
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Dankwoord (acknowledgements)
pleasant when we were in the lab. It’s my pleasure to collaborate with you and accomplish these projects. By the way, our team’s name “Xi Jian Chui” is amazing. Dear Dr. Zeng, Ying-sheng, and Yang Wu, working with you in the CD146 and Notch1 projects were so great. I am so glad that we cooperate so smoothly and published three papers in these years. Dear Xiaofen and Jiaxin, both of you bring a lot of fun to our lab. You usually do experiments to-gether, and now you got married, what amazing!
My great gratitude to Siqi, Tiantian, Jiang Qiong, Shang Li, Yuan He, Yi Yu, Meifang, and Jie
Ma. Dear Siqi, we have known each other since 10 years ago in SUMC, and now we work
in the same department of Medical Oncology at UMCG. I am particularly grateful for the assistance given by you in my daily life and work when I am studying in Groningen. I really enjoyed our “lunch walk”, which will stay in my memory. Dear Tiantian, I appreciate that you often invited me to your home for dinner, and your delicious food definitely ease my homesickness. Dear Qiong Jiang, I am so grateful that you helped to find such a good accom-modation for me before I arrived to Groningen. Your enthusiasms, diligent, and optimistic attitude to life really impressed me. It was so fun to travel around Europe with you. Dear Shang Li, you are an expert in bioinformatics analysis and thanks for teaching me how to use public database; You are smart with a good sense of humor; You always bring a lot of fun to everyone hanging out with you. Dear Yi Yu, my “lao tie”. You are definitely a good leader; Thanks for leading us to Winterberg for skiing which was a fantastic and unforgettable trip. In addition, it’s my great honor to invite you to be one of my paranymphs. Dear Yuan He, I really appreciate that you always do me a favor when I met some trouble in MOL. I keep wonderful memories for going to the music festival and having a big dinner at your home. Dear Meifang, I am grateful that you usually give such helpful advices to me for my future career. Dear Jie Ma, I wish you gain a great achievement in your research and have a good time in Groningen.
I would like to express my appreciation for Gert Jan, Nienke, Annechien, Elles, Illse, Linda,
Phuong, Marieke, and Mark who help me a lot in the lab. Dear Gert Jan, It was so amazing
that a man from a city 10 thousand kilometers away being your office mate in G1.15 of UMCG. I have appreciated your help to solve many Dutch document reading and teach me how to speak Dutch, especially how to pronounce “G”. In addition, I would like to thank your wife Tineke for making the TMA slides available to me. Dear Nienke, it’s always my pleasure to boil water for you to make tea. I am so happy that you have such cute baby. Dear An-nechien, thank you for helping me to scan the IHC slides. Elles and Ilse are very kind-heated girls; thanks for helping me to take out or put cells in liquid N2 all the time. Dear Phong, I appreciated that you helped me cutting paraffin slides. Meanwhile, the spring rolls you made were super delicious. Dear Marieke, thanks for teaching me to make the cell paraffin block. Dear Mark, thank you very much for preparing so many experimental supplies for us. I would like to thank all the collaborators, Prof. Patrick van Rijn, and Tjitze van der Land from Department of BioMedical Engineering for the mechanotransduction collaborating project; Dr. Lara Barazzuol and Daniëlle Voshart from Department of Radiation Oncology for collaborating the brain organoid project. I was so excited when we saw the 3D movie of glioblastoma cells infiltrating the brain organoid, what amazing!
I would like to pay special thankfulness, warmth and appreciation to my friends from SUMC:
Kunliang Qiu, Zhiqiang Guan, Mingzan Zhuang, Zemian, Wei Dong, Jiacong Wei, Dandan Wu, Zhijun Zeng, Xiaojuan Zhao, Congzhuo Jia, Jie Ma, Pei Meng, Minghui Li, Zhen He, Liang Du, Xiugrong Ke, Yusheng Lin, Yu Zhang, Xueling Lu, and Xiaowei Chong.
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Dankwoord (acknowledgements)
establishing the Chinese choir of Groningen. Both of you spend a lot of attentions, patience, and enthusiasm to organize our rehearsals. We all love music and music bring us together. I wish to acknowledge our choir members: Jingwen, Chenglong, Li Shang, Yang Fan, Yanni,
Wu Yi, Yu Yi, Tingli, Feng Shuai, Li Shuang, Jiang Bin, Cancan, Qinghong, Wang Lu, Li Chan, Bingrun, Huatang, Xiaojing, Yingqiu, Xiaocui, Ziwei, Liangzi, Manyun, Wenqing, Huang-ting, Yangyang, Guangcai, Huimin,Yanzhe, and Dianxi.
I would like to offer my special thanks to the Chinese friends I met when studying in Gronin-gen. Yuan He, Xin Zhao, Min Wang, Lu Wang, Yanyan Fu, Shipeng Chen, Yichen Liu,
Sheng-nan Hao, Fubiao Niu, Peijia Jiang, Wangzhao Song, Fang Liu, Yingying Cong, Mengfan Zhang, Yang Zhang, XiaoJuan Huang, Daozheng Yang, Rui Yan, Tianhe Hao, Yang Heng, Liangming Chen, Junyue Xue, Yuji Shi, Ying Zhou, Wen Li, Yuru Liu, Jing Wang, Chao Zhang, Lin Zhou, Minpeng Liang, Weiteng Guo, Jing Li, Yu Li, Jing Zhao, Qi Chen, Junjie Jiao, Chunli Kong, Youhai Li, Xiaohong Peng, Xiaoshan Bai, Kai Gao, Weier Liu, Yating Que, Peng Wang, Zhiyong Wang, Feng Yan, Yanxi Zhang, Yana Geng, Kaisheng Zheng, Runlei Ma, Ge Sun, Liqiang Lu, Jing Wu, Mengfei Cai, Rumei Lai, Liang Yang, Ying Zhou, Haibing Wen, Lisheng Zhang, Shuo Wang, Cheng Wang.
I would like to acknowledge University of Groningen (RuG), University Medical Center
Groningen(UMCG), Graduate School of Medical Sciences (GSMS) and Shantou University Medical College (SUMC) for supporting my Ph.D. project. I would like to thank department
of Medical Oncology Laboratory (MOL) for providing me such a wonderful research envi-ronment.
Finally, I would like to express my deep and sincere gratitude to my family, for their continu-ous and unparalleled love, help and support. Dear Mom and Dad, I am truly grateful for your selfless love and support. Both of you deeply convinced me that education is a powerful instrument to change and shape our destiny. Therefore, you worked very hard and did your best to keep “bread” and “books” on the table for your five children. I’m so grateful that you’ve always stood behind me, supported my dreams, encouraged my pursuits, gone along with my interests, championed my decisions, and guided me in the right direction. Without the inspiration, love, and support that you have given me, I would not have been the person I am today.
Dear Grandma and Grandpa, you’ve endured many hardships in that turbulent times, how-ever, you always have supported each other and filled your heart with hope, which really inspired me since I was young. I think my grandpa is the most wise and insightful man be-cause he married my grandma.
Dear father-in-law and mother-in-law, you are so kind and always prepare plenty of mouth-watering, delicious food whenever I visit you. I am very grateful that you brought up such a wonderful daughter and gave her hand to me. Thanks for your trust.
Special thanks should be given to my brother and sisters Wenke, Huiping, Xiqiong, and
Cuiping. Thanks to them, my childhood was never lonely and full of joy. We grow up
togeth-er, and we support each other.
My special thanks are extended to Xiaohong, Yubin, Xiaona, Juncheng, Xiaoyan, Hanhong,
Yusheng, Zewan, Chunyan, Haochun, Chunling, Zetao, Guorui, Jingya, Chuanglong, Shui-feng, Muying, Shiyang, and Chunhua. I am particularly grateful to Xiaoyan and Hanhong for
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Dankwoord (acknowledgements)
My love, Xiaoling Zhou, it has been my luckiest moment in life to meet you at Shantou University Medical College in 2007. Both of us had the same dream: being a good doctor and help people get rid of illness. We witnessed together our youth, frustration, happiness, success, and we got our bachelor and master degree together. No one knows me better than you and I confirm that you are my one and only. My most brilliant achievement was to convince you to be my wife and to share the rest of your life with me. Thanks for being my biggest supporter in my journey of Ph.D. Whenever I am down, you are always the first one to give me a hug and encouragement. When I reach a higher milestone and make progress, you are happier than anyone. As an Obstetrician and Gynaecologist, you took good care of yourself during pregnancy and prepared everything to welcome our baby. You are really a super hero! We had our beautiful daughter in my second year of PhD, you can’t image how excited I am when I met our “NO.1”. When I was studying in Groningen, you took good care of yourself and our daughter. Without you and Yanzhi’s support and encouragement, I couldn’t have finished my PhD project on time. No words can express my appreciation to you. My love for you is a journey starting at forever and ending at never. My beloved daugh-ter Yanzhi, Mom and Dad are so grateful to have you in our lives and you bring us so much joy and happiness. We hope you have a healthy and happy life. Thank you for teaching me how to be a father and I will do my very best for this job.
