4. Boareto M, Jolly MK, Goldman A et al (2016)
Notch-Jagged signalling can give rise to clusters of cells exhibiting a hybrid epithelial/mesenchymal phenotype. J R Soc Interface 13.
https://doi.org/10.1098/rsif.2015.1106
5. Li X, Jolly MK, George JT et al (2019)
Computational modeling of the crosstalk
between macrophage polarization and tumor
cell plasticity in the tumor microenvironment.
Front Oncol 9:10. https://doi.org/10.3389/
fonc.2019.00010
6. Grosse-Wilde A, Kuestner RE, Skelton SM et al
(2018) Loss of inter-cellular cooperation by
complete epithelial-mesenchymal transition
supports favorable outcomes in basal breast
cancer patients. Oncotarget 9:20018–20033.
https://doi.org/10.18632/oncotarget.25034
7. Neelakantan D, Zhou H, Oliphant MUJ et al
(2017) EMT cells increase breast cancer metastasis via paracrine GLI activation in neighbouring tumour cells. Nat Commun 8:15773.
https://doi.org/10.1038/ncomms15773
8. Nieto MA, Huang RY-J, Jackson RA, Thiery
JP (2016) EMT: 2016. Cell 166:21–45.
https://doi.org/10.1016/j.cell.2016.06.028
9. Lu M, Jolly MK, Levine H et al (2013)
MicroRNA-based regulation of epithelial–hybrid–mesenchymal fate determination. Proc
Natl Acad Sci 110:18144–18149. https://
doi.org/10.1073/pnas.1318192110
10. Font-Clos F, Zapperi S, La Porta CAM (2018)
Topography of epithelial–mesenchymal plasticity. Proc Natl Acad Sci 115:5902–5907.
https://doi.org/10.1073/pnas.1722609115
11. Steinway SN, Zanudo JGT, Ding W et al
(2014) Network modeling of TGF signaling
in hepatocellular carcinoma epithelial-to-mesenchymal transition reveals joint sonic hedgehog and Wnt pathway activation. Cancer Res
74:5963–5977.
https://doi.org/10.1158/
0008-5472.CAN-14-0225
12. Celia `-Terrassa T, Bastian C, Liu D et al (2018)
Hysteresis control of epithelial-mesenchymal
transition dynamics conveys a distinct program
with enhanced metastatic ability. Nat Commun
9:5005. https://doi.org/10.1038/s41467018-07538-7
13. Tian X-J, Zhang H, Xing J (2013) Coupled
reversible and irreversible bistable switches
underlying TGFβ-induced epithelial to mesenchymal transition. Biophys J 105:1079–1089.
https://doi.org/10.1016/j.bpj.2013.07.011
14. Hong T, Watanabe K, Ta CH et al (2015) An
Ovol2-Zeb1 mutual inhibitory circuit governs
bidirectional and multi-step transition between
epithelial and mesenchymal states. PLoS
Comput Biol 11:e1004569. https://doi.org/
10.1371/journal.pcbi.1004569
15. Jolly MK, Levine H (2017) Computational
systems biology of epithelial-hybrid-mesenchymal transitions. Curr Opin Syst Biol 3:1–6.
https://doi.org/10.1016/j.coisb.2017.02.
004
16. Pastushenko I, Brisebarre A, Sifrim A et al
(2018) Identification of the tumour transition
states occurring during EMT. Nature
556:463–468.
https://doi.org/10.1038/
s41586-018-0040-3
17. Ruscetti M, Dadashian EL, Guo W et al (2016)
HDAC
inhibition
impedes
epithelialmesenchymal plasticity and suppresses metastatic, castration-resistant prostate cancer.
Oncogene 35:3781–3795. https://doi.org/
10.1038/onc.2015.444
18. Karacosta LG, Anchang B, Ignatiadis N, et al
(2019) Mapping lung cancer epithelialmesenchymal transition states and trajectories
with single-cell resolution. bioRxiv 570341.
https://doi.org/10.1101/570341
19. Jolly MK, Huang B, Lu M et al (2014)
Towards elucidating the connection between
epithelial-mesenchymal transitions and stemness. J R Soc Interface 11:20140962. https://
doi.org/10.1098/rsif.2014.0962
20. Grosse-Wilde A, d’He ´roue ¨l AF, McIntosh E
et al (2015) Stemness of the hybrid epithelial/mesenchymal state in breast cancer and its
association with poor survival. PLoS One 10:
e0126522. https://doi.org/10.1371/journal.
pone.0126522
21. Kro ¨ger C, Afeyan A, Mraz J et al (2019) Acquisition of a hybrid E/M state is essential for
tumorigenicity of basal breast cancer cells.
Proc Natl Acad Sci 116:7353–7362. https://
doi.org/10.1073/pnas.1812876116
22. Bierie B, Pierce SE, Kroeger C et al (2017)
Integrin-β4 identifies cancer stem cell-enriched
populations of partially mesenchymal carcinoma cells. Proc Natl Acad Sci 114:
E2337–E2346.
https://doi.org/10.1073/
pnas.1618298114
23. Drubin DG, Oster G (2010) Experimentalist
meets theoretician: a tale of two scientific cultures. Mol Biol Cell 21:2099–2101. https://
doi.org/10.1091/mbc.e10-02-0143
24. Igoshin O, Chen J, Xing J et al (2019) Biophysics at the coffee shop: lessons learned
working with George Oster. Mol Biol Cell 30
(16):1882
25. Albert R, Thakar J (2014) Boolean modeling: a
logic-based dynamic approach for understanding signaling and regulatory networks and for
making useful predictions. Wiley Interdiscip
410
Shubham Tripathi et al.
Notch-Jagged signalling can give rise to clusters of cells exhibiting a hybrid epithelial/mesenchymal phenotype. J R Soc Interface 13.
https://doi.org/10.1098/rsif.2015.1106
5. Li X, Jolly MK, George JT et al (2019)
Computational modeling of the crosstalk
between macrophage polarization and tumor
cell plasticity in the tumor microenvironment.
Front Oncol 9:10. https://doi.org/10.3389/
fonc.2019.00010
6. Grosse-Wilde A, Kuestner RE, Skelton SM et al
(2018) Loss of inter-cellular cooperation by
complete epithelial-mesenchymal transition
supports favorable outcomes in basal breast
cancer patients. Oncotarget 9:20018–20033.
https://doi.org/10.18632/oncotarget.25034
7. Neelakantan D, Zhou H, Oliphant MUJ et al
(2017) EMT cells increase breast cancer metastasis via paracrine GLI activation in neighbouring tumour cells. Nat Commun 8:15773.
https://doi.org/10.1038/ncomms15773
8. Nieto MA, Huang RY-J, Jackson RA, Thiery
JP (2016) EMT: 2016. Cell 166:21–45.
https://doi.org/10.1016/j.cell.2016.06.028
9. Lu M, Jolly MK, Levine H et al (2013)
MicroRNA-based regulation of epithelial–hybrid–mesenchymal fate determination. Proc
Natl Acad Sci 110:18144–18149. https://
doi.org/10.1073/pnas.1318192110
10. Font-Clos F, Zapperi S, La Porta CAM (2018)
Topography of epithelial–mesenchymal plasticity. Proc Natl Acad Sci 115:5902–5907.
https://doi.org/10.1073/pnas.1722609115
11. Steinway SN, Zanudo JGT, Ding W et al
(2014) Network modeling of TGF signaling
in hepatocellular carcinoma epithelial-to-mesenchymal transition reveals joint sonic hedgehog and Wnt pathway activation. Cancer Res
74:5963–5977.
https://doi.org/10.1158/
0008-5472.CAN-14-0225
12. Celia `-Terrassa T, Bastian C, Liu D et al (2018)
Hysteresis control of epithelial-mesenchymal
transition dynamics conveys a distinct program
with enhanced metastatic ability. Nat Commun
9:5005. https://doi.org/10.1038/s41467018-07538-7
13. Tian X-J, Zhang H, Xing J (2013) Coupled
reversible and irreversible bistable switches
underlying TGFβ-induced epithelial to mesenchymal transition. Biophys J 105:1079–1089.
https://doi.org/10.1016/j.bpj.2013.07.011
14. Hong T, Watanabe K, Ta CH et al (2015) An
Ovol2-Zeb1 mutual inhibitory circuit governs
bidirectional and multi-step transition between
epithelial and mesenchymal states. PLoS
Comput Biol 11:e1004569. https://doi.org/
10.1371/journal.pcbi.1004569
15. Jolly MK, Levine H (2017) Computational
systems biology of epithelial-hybrid-mesenchymal transitions. Curr Opin Syst Biol 3:1–6.
https://doi.org/10.1016/j.coisb.2017.02.
004
16. Pastushenko I, Brisebarre A, Sifrim A et al
(2018) Identification of the tumour transition
states occurring during EMT. Nature
556:463–468.
https://doi.org/10.1038/
s41586-018-0040-3
17. Ruscetti M, Dadashian EL, Guo W et al (2016)
HDAC
inhibition
impedes
epithelialmesenchymal plasticity and suppresses metastatic, castration-resistant prostate cancer.
Oncogene 35:3781–3795. https://doi.org/
10.1038/onc.2015.444
18. Karacosta LG, Anchang B, Ignatiadis N, et al
(2019) Mapping lung cancer epithelialmesenchymal transition states and trajectories
with single-cell resolution. bioRxiv 570341.
https://doi.org/10.1101/570341
19. Jolly MK, Huang B, Lu M et al (2014)
Towards elucidating the connection between
epithelial-mesenchymal transitions and stemness. J R Soc Interface 11:20140962. https://
doi.org/10.1098/rsif.2014.0962
20. Grosse-Wilde A, d’He ´roue ¨l AF, McIntosh E
et al (2015) Stemness of the hybrid epithelial/mesenchymal state in breast cancer and its
association with poor survival. PLoS One 10:
e0126522. https://doi.org/10.1371/journal.
pone.0126522
21. Kro ¨ger C, Afeyan A, Mraz J et al (2019) Acquisition of a hybrid E/M state is essential for
tumorigenicity of basal breast cancer cells.
Proc Natl Acad Sci 116:7353–7362. https://
doi.org/10.1073/pnas.1812876116
22. Bierie B, Pierce SE, Kroeger C et al (2017)
Integrin-β4 identifies cancer stem cell-enriched
populations of partially mesenchymal carcinoma cells. Proc Natl Acad Sci 114:
E2337–E2346.
https://doi.org/10.1073/
pnas.1618298114
23. Drubin DG, Oster G (2010) Experimentalist
meets theoretician: a tale of two scientific cultures. Mol Biol Cell 21:2099–2101. https://
doi.org/10.1091/mbc.e10-02-0143
24. Igoshin O, Chen J, Xing J et al (2019) Biophysics at the coffee shop: lessons learned
working with George Oster. Mol Biol Cell 30
(16):1882
25. Albert R, Thakar J (2014) Boolean modeling: a
logic-based dynamic approach for understanding signaling and regulatory networks and for
making useful predictions. Wiley Interdiscip
410
Shubham Tripathi et al.