Received: 22 September 2018
|
Accepted: 7 December 2018
DOI: 10.1002/jcp.28160
REVIEW ARTICLE
The basics of epithelial–mesenchymal transition (EMT):
A study from a structure, dynamics, and functional
perspective
Vishal Das
1
| Sourya Bhattacharya
2
| Channakeshavaiah Chikkaputtaiah
1
|
Saugata Hazra
2
| Mintu Pal
1
1
Biological Sciences and Technology Division
(Biotechnology Group), CSIR‐North East
Institute of Science and Technology, Academy
of Scientific and Innovative Research, Jorhat,
Assam, India
2
Department of Biotechnology, Centre for
Nanotechnology, Indian Institute of
Technology Roorkee (IITR), Roorkee,
Uttarakhand, India
Correspondence
Dr. Saugata Hazra, Department of
Biotechnology, Centre for Nanotechnology,
Indian Institute of Technology Roorkee (IITR),
Roorkee, Uttarakhand 247667, India.
Email: shazrfbt@iitr.ac.in
Dr. Mintu Pal, Biological Sciences and
Technology Division (Biotechnology Group),
CSIR‐North East Institute of Science and
Technology, Academy of Scientific and
Innovative Research, Jorhat, Assam 785006,
India.
Email: mpal24@yahoo.com
Funding information
SERB‐DST, Govt. of India, Grant/Award
Number: SB/S2/RJN‐087/2014
Abstract
Epithelial–mesenchymal transition (EMT) is a key step in transdifferentiation process
in solid cancer development. Forthcoming evidence suggest that the stratified
program transforms polarized, immotile epithelial cells to migratory mesenchymal
cells associated with enhancement of breast cancer stemness, metastasis, and drug
resistance. It involves primarily several signaling pathways, such as transforming
growth factor‐β (TGF‐β), cadherin, notch, plasminogen activator protein inhibitor,
urokinase plasminogen activator, and WNT/beta catenin pathways. However, current
understanding on the crosstalk of multisignaling pathways and assemblies of key
transcription factors remain to be explored. In this review, we focus on the crosstalk
of signal transduction pathways linked to the current therapeutic and drug
development strategies. We have also performed the computational modeling on
indepth the structure and conformational dynamic studies of regulatory proteins and
analyze molecular interactions with their associate factors to understand the
complicated process of EMT in breast cancer progression and metastasis. Electro-
static potential surfaces have been analyzed that help in optimization of electrostatic
interactions between the protein and its ligand. Therefore, understanding the
biological implications underlying the EMT process through molecular biology with
biocomputation and structural biology approaches will enable the development of
new therapeutic strategies to sensitize tumors to conventional therapy and suppress
their metastatic phenotype.
KEYWORDS
EMT, matrix metalloproteinases, signaling pathways, stem cells, structure and dynamics studies,
transformation growth factor‐β (TGF‐β)
1 | INTRODUCTION
Breast cancer is the most common cancer in women globally,
whereas about 90% of death of patients with breast cancer is caused
by invasion and metastasis that are two important features of
epithelial–mesenchymal transition (EMT) (Pantel & Brakenhoff,
2004; Elzamly et al., 2018; Sotiriou et al., 2003). EMT is link up
with a loosening of intracellular tight junctions and disruption of
contact between cell to cell, hence the cells acquire the mesenchymal
morphology. After that, the cells gain the ability to renew themselves
and to increase in heterogeneous subpopulation which amplifies
motility of the cells after which it releases cells from the site of origin.
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