This slide is about role of EMT in cancer metastasis, how EMT plays a critical role in metastatic tumor development and in the last part of the slide we discuss about the role of EMT in embryonic development purpose. Slide no 1 : Describes about epithelial to mesenchymal transition. Slide no 2: Describes about molecular markers of epithelial cell and mesenchymal cell. Slide no 3 : Describes about transcription factors that induce EMT Slide no 4 : Describes about how different transcription factors will function Slide no 5 : Describes about roll of micro- RNAs in EMT Slide no 6 and 7 : Describes about signaling pathways involve in EMT Slide no 8 : Describes about roll of EMT in tumor metastasis Slide no 9 : Describes about roll of EMT in tumor microenvironment Slide no 10 and 11 : Describes about roll of EMT in embryonic development

1. The Epithelial-
to-Mesenchymal
Transition (EMT)
in Cancer
Arka Laha
Semester 5th
Session 2019-20
B.Sc in Microbiology
Registration Number KNU19111001115
Depertment of Microbiology
Michael Madhusudan Memorial College

2. Epithelial to mesenchymal transition :
Reference : Nieto MA, Huang RY, Jackson RA, Thiery JP. EMT: 2016. Cell. 2016 Jun 30;166(1):21-45. doi:
10.1016/j.cell.2016.06.028. PMID: 27368099.

3. Molecular markers of Epithelial cells and Mesenchymal cells :
● Cells have front back
polarity
● Cells have apico- basal
polarity
Reference:Dongre A, Weinberg RA. New insights into the mechanisms of epithelial-mesenchymal transition and implications for
cancer. Nat Rev Mol Cell Biol. 2019 Feb;20(2):69-84. doi: 10.1038/s41580-018-0080-4. PMID: 30459476.

4. Transcription factors that induce EMT :
Signals of EMT
EMT inducing transcription
factors :
Snail1,Snail2,ZEB1,ZEB2,Twist1,
Twist2, LEF-1
Inhibit the epithelial gene
expression and activate the
mesenchymal gene expression
GENE
Regulatory sequence
Activated
transcription
factor
External signals
Gene expression
modulation
m- RNA
Protein
● Transcription
factors can both
activator as well
as repressor
Reference : Gonzalez DM, Medici D. Signaling mechanisms of the
epithelial-mesenchymal transition. Sci Signal. 2014 Sep 23;7(344):re8.
doi: 10.1126/scisignal.2005189. PMID: 25249658; PMCID: PMC4372086.

5. How transcription factors will function :
SNAIL
(Snail1,Snail2)
Twist1,Twist2
ZEB
(ZEB1 and ZEB2
LEF -1
Repress the
transcription of
E.cadherin by
binding with the
promoter region of
CDH1 gene
Twist1 + BMI 1
polycomb group
repressor complex
protein acts on E-
cadherin and inhibit
p16INK4aplha , also
repress several mi-
RNAs (HOXD1
Inhibition)
Repress the CDH1 gene
work on E-Box promoter ,
co-operate with
deacetylase sirtuin1
modifying histone H3 and
reduce the binding of RNA
pol ii at the CDH1 promoter
, repress the plakophilin-2
and ZO-3 dis association
of adherens junction
It directly induce
EMT repress the
expression of E-
cadherin and
also active the
beta - catenin

6. Roll of micro-RNAs in EMT :
TWIST1
SNAIL2
ZEB
SNAIL1
miRNA-30
miRNA-29
miRNA-203
miRNA-34
miRNA-200
miRNA-205
miRNA-203
miRNA-204

7. Signaling Pathways involve in EMT :
Gene expression of
vimentin ,fibronectin
,SNAILN,SLUG,ZEB,TWI
T

8. Signaling Pathways involve in EMT :

9. EMT in tumor metastisis :
Reference: Mittal V. Epithelial Mesenchymal Transition in Tumor Metastasis. Annu Rev Pathol. 2018 Jan
24;13:395-412. doi: 10.1146/annurev-pathol-020117-043854. PMID: 29414248.

10. Tumor microenvironment and EMT :
● Inflammation as an
inducer of tumor EMT :
TAMs produced TNF-
alph ,IL-1
● Role of hypoxia and
oxidative stress in EMT
:HIF signals the
activation of Snail,
mitochondria produce
ROS in this induce
cancer in certain cells
Reference :Epithelial-Mesenchymal Transition in tumor
microenvironment .Yingying Jing, Zhipeng Han, Shanshan Zhang, Yan
Liu and Lixin Wei*

11. Reference: Role of the epithelial–mesenchymal transition and its effects on embryonic stem cells Ye-Seul Kim1,
Bo-Rim Yi1, Nam-Hyung Kim2 and Kyung-Chul Choi1
EMT and development :

13. Thank you