Mechanoregulation of angiopoietin-like 4 in epithelial-mesenchymal transition and cancer metastasis
Author: Liao, Zehuan
Date: 2023-12-07
Location: Lecture Room 205, Karolinska Institutet, Solna (Hybrid Format)
Time: 09.30
Department: Inst för mikrobiologi, tumör- och cellbiologi / Dept of Microbiology, Tumor and Cell Biology
Abstract
The epithelial-mesenchymal transition (EMT) serves as a pivotal mechanism in the
progression of metastatic cancer. However, current research, predominantly
reliant on 2D monolayer cultures, inadequately replicates the intricate nature of a
3D tumor microenvironment. In the main project (Paper I), we investigated the
transcriptomes of various cancer cell types undergoing EMT in both 2D and 3D
cultures with different EMT inducers. We identified a 3D EMT gene signature that
has broad implications across different types of human cancers. Angiopoietin-like
4 protein (ANGPTL4) was found to be a top ranked hub gene with clinical
relevance and impact. Our study also revealed the mechanoregulation of
ANGPTL4, which corroborated with its high expression in advanced tumors.
Consistently, ANGPTL4 deficiency attenuated primary tumor growth and EMT of
cancer cells. These findings suggest that targeting ANGPTL4 may be a promising
approach to inhibit EMT and prevent cancer progression. In the collaborative
project (Paper II), we studied the regulation of membrane microenvironment and
signal transduction in natural killer (NK) cells, a group of innate immune cells
involved in the tumor microenvironment (TME) and cancer immunotherapy. Here,
we revealed the PIP2-regulated recruitment of DAP12 homodimer to lipid raft
boundary of NK cells. In another collaborative project (Paper III), we introduce
HTCA, a single-cell RNA-sequencing database with various user-friendly analysis
tools. Collectively, our main findings reflect the intricate regulation of physical
stiffness within the TME influencing EMT signaling in cancer cells, where ANGPTL4
emerges as a crucial player. Our comprehensive analyses strongly underscore the
clinical significance of ANGPTL4, particularly in advanced stage cancer, aligning
with our broader understanding of tumors in patients. In essence, our study vividly
demonstrates how the TME's stiffness orchestrates the mechanoregulation of
ANGPTL4, a hub gene within the 3D EMT gene signature.
List of papers:
I. Zehuan Liao, Joseph Jing Heng Lim, Jeannie Xue Ting Lee, Marcus Ivan Gerard Vos, Damien Chua, Yun Sheng Yip, Choon Boon Too, Huan Cao, Jun Kit Wang, Yufeng Shou, Andy Tay, Kaisa Lehti, Hong Sheng Cheng, Chor Yong Tay, Nguan Soon Tan. "Attenuating epithelial-to-mesenchymal transition in cancer through angiopoietin-like 4 inhibition in a 3D tumor microenvironment model." [Manuscript]
Fulltext (DOI)
Pubmed
II. Ruijuan Dong, Yan Tan, Angran Fan, Zehuan Liao, Hangrui Liu, and Peng Wei. "Molecular dynamics of the recruitment of immunoreceptor signaling module DAP12 homodimer to lipid raft boundary regulated by PIP2." The Journal of Physical Chemistry B. 124, no. 3 (2019): 504-510.
Fulltext (DOI)
Pubmed
View record in Web of Science®
III. Lu Pan, Shaobo Shan, Roman Tremmel, Weiyuan Li, Zehuan Liao, Hangyu Shi, Qishuang Chen, Xiaolu Zhang, and Xuexin Li. "HTCA: a database with an in-depth characterization of the single-cell human transcriptome." Nucleic Acids Research. 51, no. D1 (2023): D1019- D1028.
Fulltext (DOI)
Pubmed
View record in Web of Science®
I. Zehuan Liao, Joseph Jing Heng Lim, Jeannie Xue Ting Lee, Marcus Ivan Gerard Vos, Damien Chua, Yun Sheng Yip, Choon Boon Too, Huan Cao, Jun Kit Wang, Yufeng Shou, Andy Tay, Kaisa Lehti, Hong Sheng Cheng, Chor Yong Tay, Nguan Soon Tan. "Attenuating epithelial-to-mesenchymal transition in cancer through angiopoietin-like 4 inhibition in a 3D tumor microenvironment model." [Manuscript]
Fulltext (DOI)
Pubmed
II. Ruijuan Dong, Yan Tan, Angran Fan, Zehuan Liao, Hangrui Liu, and Peng Wei. "Molecular dynamics of the recruitment of immunoreceptor signaling module DAP12 homodimer to lipid raft boundary regulated by PIP2." The Journal of Physical Chemistry B. 124, no. 3 (2019): 504-510.
Fulltext (DOI)
Pubmed
View record in Web of Science®
III. Lu Pan, Shaobo Shan, Roman Tremmel, Weiyuan Li, Zehuan Liao, Hangyu Shi, Qishuang Chen, Xiaolu Zhang, and Xuexin Li. "HTCA: a database with an in-depth characterization of the single-cell human transcriptome." Nucleic Acids Research. 51, no. D1 (2023): D1019- D1028.
Fulltext (DOI)
Pubmed
View record in Web of Science®
Institution: Karolinska Institutet
Supervisor: Lehti, Kaisa
Co-supervisor: Tan, Nguan Soon; Selivanova, Galina
Issue date: 2023-11-13
Rights:
Publication year: 2023
ISBN: 978-91-8017-159-5
Statistics
Total Visits
Views | |
---|---|
Mechanoregulation ... | 415 |
Total Visits Per Month
October 2023 | November 2023 | December 2023 | January 2024 | February 2024 | March 2024 | April 2024 | |
---|---|---|---|---|---|---|---|
Mechanoregulation ... | 0 | 277 | 72 | 24 | 25 | 11 | 6 |
File Visits
Views | |
---|---|
Thesis_Zehuan_Liao.pdf | 517 |
Cover Zehuan Liao.pdf | 85 |
Top country views
Views | |
---|---|
United States | 91 |
Singapore | 83 |
Hong Kong | 51 |
Sweden | 51 |
China | 36 |
Germany | 11 |
India | 8 |
Norway | 7 |
United Kingdom | 6 |
Japan | 5 |
Top cities views
Views | |
---|---|
Singapore | 71 |
Stockholm | 19 |
Boydton | 17 |
Central | 16 |
Sundbyberg | 9 |
Taipei | 5 |
Leyburn | 4 |
Malmo | 4 |
Piscataway | 4 |
San Mateo | 4 |