A landscape view on the interplay between EMT and cancer metastasis

NPJ Systems Biology and Applications
Chunhe Li, Gabor Balazsi

Abstract

The epithelial-mesenchymal transition (EMT) is a basic developmental process that converts epithelial cells to mesenchymal cells. Although EMT might promote cancer metastasis, the molecular mechanisms for it remain to be fully clarified. To address this issue, we constructed an EMT-metastasis gene regulatory network model and quantified the potential landscape of cancer metastasis-promoting system computationally. We identified four steady-state attractors on the landscape, which separately characterize anti-metastatic (A), metastatic (M), and two other intermediate (I1 and I2) cell states. The tetrastable landscape and the existence of intermediate states are consistent with recent single-cell measurements. We identified one of the two intermediate states I1 as the EMT state. From a MAP approach, we found that for metastatic progression cells need to first undergo EMT (enter the I1 state), and then become metastatic (switch from the I1 state to the M state). Specifically, for metastatic progression, EMT genes (such as ZEB) should be activated before metastasis genes (such as BACH1). This suggests that temporal order is important for the activation of cellular programs in biological systems, and provides a possible mechanism of...Continue Reading

References

Dec 13, 1991·Science·H FrauenfelderP G Wolynes
Jun 1, 1971·Journal of Theoretical Biology·S Kauffman
Jan 27, 2000·Cell·D Hanahan, R A Weinberg
Jul 5, 2001·Proceedings of the National Academy of Sciences of the United States of America·M Thattai, A van Oudenaarden
Sep 19, 2002·Proceedings of the National Academy of Sciences of the United States of America·Peter S SwainEric D Siggia
Feb 28, 2003·Proceedings of the National Academy of Sciences of the United States of America·Masaki Sasai, Peter G Wolynes
May 11, 2005·Nature Reviews. Genetics·Mads KaernJames J Collins
Mar 19, 2008·The Journal of Chemical Physics·Xiang ZhouWeinan E
Aug 23, 2008·Proceedings of the National Academy of Sciences of the United States of America·Jin WangErkang Wang
Dec 20, 2008·Journal of the Royal Society, Interface·Melissa Vellela, Hong Qian
Jul 15, 2009·Seminars in Cell & Developmental Biology·Sui HuangStuart Kauffman
Dec 1, 2009·Cell·Jean Paul ThieryM Angela Nieto
Mar 23, 2010·Bulletin of Mathematical Biology·David F AndersonThomas G Kurtz
Apr 16, 2010·Proceedings of the National Academy of Sciences of the United States of America·Jin WangErkang Wang
Dec 30, 2010·The Journal of Physical Chemistry. B·Haidong FengJin Wang
Feb 9, 2011·Physical Biology·P C W Davies, C H Lineweaver
Mar 8, 2011·Cell·Douglas Hanahan, Robert A Weinberg
May 4, 2011·Proceedings of the National Academy of Sciences of the United States of America·Jin WangErkang Wang
Jul 12, 2011·Annual Review of Cell and Developmental Biology·M Angela Nieto
Apr 20, 2012·Nature Reviews. Cancer·Andriy MarusykKornelia Polyak
Jun 9, 2012·Current Biology : CB·James E Ferrell
Aug 10, 2012·The Journal of Biological Chemistry·Yajun LiangYibin Kang
Aug 11, 2012·Progress in Brain Research·Sato HonmaKen-Ichi Honma
Sep 12, 2012·Nature Biotechnology·Pau CreixellRune Linding
Mar 7, 2013·Cancer Letters·Yukiko Nakaya, Guojun Sheng
May 7, 2013·The Journal of Physical Chemistry. B·Chen Liao, Ting Lu
Sep 10, 2013·Nature Medicine·Thomas BrabletzZena Werb
Oct 25, 2013·Proceedings of the National Academy of Sciences of the United States of America·Mingyang LuEshel Ben-Jacob
Jan 8, 2014·Proceedings of the National Academy of Sciences of the United States of America·Jiyoung LeeMarsha Rich Rosner
Jun 21, 2014·Proceedings of the National Academy of Sciences of the United States of America·Bin Zhang, Peter G Wolynes
Aug 30, 2014·Physical Review Letters·Mingyang LuEshel Ben-Jacob
Sep 4, 2014·Cancer Research·Mingyang LuEshel Ben-Jacob
Sep 18, 2014·Proceedings of the National Academy of Sciences of the United States of America·Chunhe Li, Jin Wang
Sep 19, 2014·Journal of the Royal Society, Interface·Chunhe Li, Jin Wang
Oct 24, 2014·Journal of the Royal Society, Interface·Mohit Kumar JollyEshel Ben-Jacob
Apr 9, 2015·Clinical and Translational Medicine·Sarah HeerbothSibaji Sarkar

❮ Previous
Next ❯

Citations

Dec 12, 2018·Physical Biology·Kuheli BiswasAnandamohan Ghosh
Jan 18, 2019·Physical Biology·Jorge Gómez Tejeda ZañudoRéka Albert
Mar 12, 2020·PloS One·Joseph B HubbardAnne L Plant
Aug 28, 2019·International Journal of Molecular Sciences·Natalia Glatzel-PlucińskaMarzenna Podhorska-Okołów
Aug 14, 2020·Journal of Clinical Medicine·Zihao Chen, Chunhe Li
Jul 28, 2019·Scientific Reports·Niraj KumarRahul V Kulkarni
Jun 30, 2019·Journal of Clinical Medicine·Vimalathithan Devaraj, Biplab Bose
Oct 6, 2020·Frontiers in Oncology·Ayalur Raghu SubbalakshmiMohit Kumar Jolly
Oct 27, 2020·Computational and Structural Biotechnology Journal·Anne L PlantJeffrey Stinson
Mar 5, 2020·Computational and Structural Biotechnology Journal·Xin Kang, Chunhe Li
Feb 4, 2021·ACS Synthetic Biology·Anupam Dey, Debashis Barik
Apr 4, 2021·International Journal of Molecular Sciences·Sylwia S Wilk, Katarzyna A Zabielska-Koczywąs
Jun 20, 2020·Scientific Reports·Rehab AlshargabiFusanori Nishimura
Oct 22, 2019·Molecular Pharmaceutics·Cátia DominguesAna Figueiras
Sep 4, 2021·NPJ Systems Biology and Applications·Xiang LiJianwei Shuai
Nov 6, 2021·Journal of Biological Physics·Lars Koopmans, Hyun Youk
Nov 16, 2021·Frontiers in Computational Neuroscience·Leijun Ye, Chunhe Li

❮ Previous
Next ❯

Methods Mentioned

BETA
single-cell sequencing

Software Mentioned

matlab
mathop

Related Concepts

Trending Feeds

COVID-19

Coronaviruses encompass a large family of viruses that cause the common cold as well as more serious diseases, such as the ongoing outbreak of coronavirus disease 2019 (COVID-19; formally known as 2019-nCoV). Coronaviruses can spread from animals to humans; symptoms include fever, cough, shortness of breath, and breathing difficulties; in more severe cases, infection can lead to death. This feed covers recent research on COVID-19.

Blastomycosis

Blastomycosis fungal infections spread through inhaling Blastomyces dermatitidis spores. Discover the latest research on blastomycosis fungal infections here.

Nuclear Pore Complex in ALS/FTD

Alterations in nucleocytoplasmic transport, controlled by the nuclear pore complex, may be involved in the pathomechanism underlying multiple neurodegenerative diseases including Amyotrophic Lateral Sclerosis and Frontotemporal Dementia. Here is the latest research on the nuclear pore complex in ALS and FTD.

Applications of Molecular Barcoding

The concept of molecular barcoding is that each original DNA or RNA molecule is attached to a unique sequence barcode. Sequence reads having different barcodes represent different original molecules, while sequence reads having the same barcode are results of PCR duplication from one original molecule. Discover the latest research on molecular barcoding here.

Chronic Fatigue Syndrome

Chronic fatigue syndrome is a disease characterized by unexplained disabling fatigue; the pathology of which is incompletely understood. Discover the latest research on chronic fatigue syndrome here.

Evolution of Pluripotency

Pluripotency refers to the ability of a cell to develop into three primary germ cell layers of the embryo. This feed focuses on the mechanisms that underlie the evolution of pluripotency. Here is the latest research.

Position Effect Variegation

Position Effect Variagation occurs when a gene is inactivated due to its positioning near heterochromatic regions within a chromosome. Discover the latest research on Position Effect Variagation here.

STING Receptor Agonists

Stimulator of IFN genes (STING) are a group of transmembrane proteins that are involved in the induction of type I interferon that is important in the innate immune response. The stimulation of STING has been an active area of research in the treatment of cancer and infectious diseases. Here is the latest research on STING receptor agonists.

Microbicide

Microbicides are products that can be applied to vaginal or rectal mucosal surfaces with the goal of preventing, or at least significantly reducing, the transmission of sexually transmitted infections. Here is the latest research on microbicides.